To see the other types of publications on this topic, follow the link: NF-ĸB.
Journal articles on the topic 'NF-ĸB'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'NF-ĸB.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Tegtmeyer, Nicole, Delara Soltan Esmaeili, Irshad Sharafutdinov, Jakob Knorr, Michael Naumann, Thomas Alter, and Steffen Backert. "Importance of cortactin for efficient epithelial NF-ĸB activation by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa, but not Campylobacter spp." European Journal of Microbiology and Immunology 11, no. 4 (February 3, 2022): 95–103. http://dx.doi.org/10.1556/1886.2021.00023.
Full textAbstract:
Abstract Transcription factors of the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF-ĸB) family control important signaling pathways in the regulation of the host innate immune system. Various bacterial pathogens in the human gastrointestinal tract induce NF-ĸB activity and provoke pro-inflammatory signaling events in infected epithelial cells. NF-ĸB activation requires the phosphorylation-dependent proteolysis of inhibitor of ĸB (IĸB) molecules including the NF-ĸB precursors through ubiquitin-mediated proteolysis. The canonical NF-ĸB pathway merges on IĸB kinases (IKKs), which are required for signal transduction. Using CRISPR-Cas9 technology, secreted embryonic alkaline phosphatase (SEAP) reporter assays and cytokine enzyme-linked immunosorbent assay (ELISA), we demonstrate that the actin-binding protein cortactin is involved in NF-ĸB activation and subsequent interleukin-8 (IL-8) production upon infection by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa. Our data indicate that cortactin is needed to efficiently activate the c-Sarcoma (Src) kinase, which can positively stimulate NF-ĸB during infection. In contrast, cortactin is not involved in activation of NF-ĸB and IL-8 expression upon infection with Campylobacter species C. jejuni, C. coli or C. consisus, suggesting that Campylobacter species pluralis (spp.) induce a different signaling pathway upstream of cortactin to trigger the innate immune response.
2
Mitxitorena, Izaskun, Domenico Somma, Jennifer P. Mitchell, Matti Lepistö, Christian Tyrchan, Emma L. Smith, Patrick A. Kiely, Helen Walden, Karen Keeshan, and Ruaidhrí J. Carmody. "The deubiquitinase USP7 uses a distinct ubiquitin-like domain to deubiquitinate NF-ĸB subunits." Journal of Biological Chemistry 295, no. 33 (June 25, 2020): 11754–63. http://dx.doi.org/10.1074/jbc.ra120.014113.
Full textAbstract:
The transcription factor NF-ĸB is a master regulator of the innate immune response and plays a central role in inflammatory diseases by mediating the expression of pro-inflammatory cytokines. Ubiquitination-triggered proteasomal degradation of DNA-bound NF-ĸB strongly limits the expression of its target genes. Conversely, USP7 (deubiquitinase ubiquitin-specific peptidase 7) opposes the activities of E3 ligases, stabilizes DNA-bound NF-ĸB, and thereby promotes NF-ĸB–mediated transcription. Using gene expression and synthetic peptide arrays on membrane support and overlay analyses, we found here that inhibiting USP7 increases NF-ĸB ubiquitination and degradation, prevents Toll-like receptor–induced pro-inflammatory cytokine expression, and represents an effective strategy for controlling inflammation. However, the broad regulatory roles of USP7 in cell death pathways, chromatin, and DNA damage responses limit the use of catalytic inhibitors of USP7 as anti-inflammatory agents. To this end, we identified an NF-ĸB–binding site in USP7, ubiquitin-like domain 2, that selectively mediates interactions of USP7 with NF-ĸB subunits but is dispensable for interactions with other proteins. Moreover, we found that the amino acids 757LDEL760 in USP7 critically contribute to the interaction with the p65 subunit of NF-ĸB. Our findings support the notion that USP7 activity could be potentially targeted in a substrate-selective manner through the development of noncatalytic inhibitors of this deubiquitinase to abrogate NF-ĸB activity.
3
Candra, Gede Ngurah Hadi, and I. Made Adnyana Partha Wijaya. "Molecular Docking Kaempferol sebagai Antiinflamasi pada Aterosklerosis secara In Silico." Jurnal Ilmiah Medicamento 7, no. 1 (March 31, 2021): 13–18. http://dx.doi.org/10.36733/medicamento.v7i1.1497.
Full textAbstract:
Aterosklerosis digambarkan sebagai reaksi inflamasi kronis dari dinding pembuluh darah sebagai respons terhadap dislipidemia bersama dengan gangguan endotel termasuk penarikan leukosit dengan aktivasi sel vaskular lokal. Gangguan endotel merangsang produksi sitokin proinflamasi dimediasi oleh NF-κΒ sehingga mendukung terbentuknya plak ateroma. Flavonol daun kelor memiliki aktivitas dalam memperlambat kejadian inflamasi. Flavonol utama pada daun kelor adalah kaempferol. Pengujian aktivitas kaempferol sebagai anti-inflamasi aterosklerosis yang didasarkan interaksi protein NF-ĸB dengan metode molecular docking. Pengujian aktivitas dilaksanakan adalah penyiapan struktur protein NF-ĸB, persiapan protein dengan Chimera1.11.1, optimasi struktur 3D kaempferol dengan HyperChem 8, validasi metode molecular docking dan docking kaempferol pada protein NF-ĸB dengan Autodock tools 1.5.6. Hasil penelitian menunjukkan bahwa kaempferol memiliki afinitas karena mampu membentuk ikatan hidrogen dengan protein NF-ĸB. Energi ikatan yang terbentuk antara kaempferol dengan protein NF-ĸB sebesar -7,85 kkal/mol yang membentuk ikatan hidrogen pada residu asam amino LEU472 dan SER476. Kaempferol mempunyai aktivitas sebagai anti-aterosklerosis karena memiliki afinitas dengan protein NF-ĸB yang dapat menghambat proses inflamasi terbentuknya plak ateroma.
4
KAMEOKA, Masanori, Katsuya OTA, Toshifumi TETSUKA, Yasuharu TANAKA, Asako ITAYA, Takashi OKAMOTO, and Koichiro YOSHIHARA. "Evidence for regulation of NF-κB by poly(ADP-ribose) polymerase." Biochemical Journal 346, no. 3 (March 7, 2000): 641–49. http://dx.doi.org/10.1042/bj3460641.
Full textAbstract:
The DNA-binding activity of NF-ĸB in nuclear extracts of poly(ADP-ribose) polymerase (PARP)-defective mutant L1210 cell clones was markedly increased and was inversely correlated with the PARP content in these cells. The DNA-binding activity of NF-ĸB in a clone with the lowest PARP content (Cl-3527, contained 6% of PARP of wild type cells) was about 35-fold of that of the wild-type cells, whereas the change in the DNA-binding activity of AP-1 and SP-1 in the mutant was relatively small or not so significant. Transfection of a PARP-expressing plasmid to the mutant cells decreased the abnormally high levels of NF-ĸB complexes, especially p50/p65(Rel A) complex, to near the normal level. Moreover, poly(ADP-ribosyl)ation of nuclear extracts in vitro suppressed the ability of NF-ĸB to form a complex with its specific DNA probe by approx. 80%. Further analysis with purified recombinant NF-ĸB proteins revealed that both rp50 and rMBP-p65 (Rel A) proteins, but not rGST-IĸB, could be poly(ADP-ribosyl)ated in vitro and that the modification resulted in a marked decrease in the DNA-binding activity of rMBP-p65, whereas a slight activation was observed in rp50. Poly(ADP-ribosyl)ated p65/NF-ĸB was detected in the cytosol of wild type L1210 cells by immunoblotting with anti-poly(ADP-ribose) and anti-p65 antibodies. Taken together, these results strongly suggest that PARP is involved in the regulation of NF-ĸB through the protein modification.
5
Theile, Dirk, Lelia Wagner, Cindy Bay, Walter Emil Haefeli, and Johanna Weiss. "Time-Resolved Effect of Interferon-Alpha 2a on Activities of Nuclear Factor Kappa B, Pregnane X Receptor and on Drug Disposition Genes." Pharmaceutics 13, no. 6 (May 28, 2021): 808. http://dx.doi.org/10.3390/pharmaceutics13060808.
Full textAbstract:
Interferon-alpha (IFN-α) is suggested to cause pharmacokinetic drug interactions by lowering expression of drug disposition genes through affecting the activities of nuclear factor kappa B (NF-ĸB) and pregnane X receptor (PXR). The time-resolved impact of IFN-α 2a (1000 U/mL; 5000 U/mL; 2 h to 30 h) on the activities of NF-ĸB and PXR and mRNA expression (5000 U/mL; 24 h, 48 h) of selected drug disposition genes and on cytochrome P450 (CYP3A4) activity in LS180 cells (5000 U/mL; 24 h, 48 h) was evaluated using luciferase-based reporter gene assays, reverse transcription polymerase chain reaction, and luminescence-based CYP3A4 activity assays. The cross-talk between NF-ĸB activation and PXR suppression was evaluated by NF-ĸB blockage (10 µM parthenolide). IFN-α 2a initially (2 h, 6 h) enhanced NF-ĸB activity 2-fold and suppressed PXR activity by 30%. mRNA of CYP3A4 was halved, whereas UGT1A1 was increased (1.35-fold) after 24 h. After 48 h, ABCB1 expression was increased (1.76-fold). CYP3A4 activity remained unchanged after 24 h, but was enhanced after 48 h (1.35-fold). IFN-α 2a demonstrated short-term suppressive effects on PXR activity and CYP3A4 mRNA expression, likely mediated by activated NF-ĸB. Longer exposure enhanced CYP3A4 activity. Clinical trials should evaluate the relevance by investigating the temporal effects of IFN-α on CYP3A4 using a sensitive marker substrate.
6
NAGARAJAN, Raman P., Feifei CHEN, Wei LI, Eva VIG, Maureen A. HARRINGTON, Harikrishna NAKSHATRI, and Yan CHEN. "Repression of transforming-growth-factor-β-mediated transcription by nuclear factor κB." Biochemical Journal 348, no. 3 (June 7, 2000): 591–96. http://dx.doi.org/10.1042/bj3480591.
Full textAbstract:
Activation of transforming growth factor-β (TGF-β) and activin receptors leads to phosphorylation of Sma- and Mad-related protein 2 (Smad2) and Smad3, which function as transcription factors to regulate gene expression. Smad7 is a regulatory protein which is able to inhibit TGF-β and activin signalling in a negative-feedback loop, mediated by a direct regulation by Smad3 and Smad4 via a Smad-binding element (SBE) in the Smad7 promoter. Interestingly, we found that the Smad7 promoter was also regulated by nuclear factor ĸB (NF-ĸB), a transcription factor which plays an important role in inflammation and the immune response. Expression of NF-ĸB p65 subunit was able to inhibit the Smad7 promoter activity, and this inhibition could be reversed by co-expression of IĸB, an inhibitor of NF-ĸB. In addition, the inhibitory activity of p65 was observed in a minimal promoter that contained only the Smad7 SBE and a TATA box, without any consensus NF-ĸB binding site. This inhibitory effect appeared to be common to other TGF-β- and activin-responsive promoters, since p65 also inhibited the forkhead-activin-signal-transducer-2-mediated activation of a Xenopus Mix.2 promoter, as well as the Smad3-mediated activation of 3TP-lux which contains PMA-responsive elements and a plasminogen-activator-inhibitor-1 promoter. Activation of endogenous NF-ĸB by tumour necrosis factor-α (TNF-α) was also able to inhibit the Smad7 promoter in human embryonic kidney 293 cells. In human hepatoma HepG2 cells, TNF-α was able to inhibit TGF-β- and activin-mediated transcriptional activation. Furthermore, overexpression of the transcription co-activator p300 could abrogate the inhibitory effect of NF-ĸB on the Smad7 promoter. Taken together, these data have indicated a novel mode of crosstalk between the Smad and the NF-ĸB signalling cascades at the transcriptional level by competing for a limiting pool of transcription co-activators.
7
D'ACQUISTO, Fulvio, Virginia LANZOTTI, and Rosa CARNUCCIO. "Cyclolinteinone, a sesterterpene from sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase protein expression by blocking nuclear factor-κB activation in J774 macrophages." Biochemical Journal 346, no. 3 (March 7, 2000): 793–98. http://dx.doi.org/10.1042/bj3460793.
Full textAbstract:
We investigated the effect of cyclolinteinone, a sesterterpene from Caribbean sponge Cacospongia linteiformis, on inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2) protein expression in lipopolysaccharide (LPS)-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 μg/ml) caused an increase of both iNOS and COX-2 protein expression, which was prevented in a concentration-dependent fashion by cyclolinteinone (12.5, 25 and 50 μM). Electrophoretic mobility-shift assay indicated that cyclolinteinone blocked the activation of nuclear factor-ĸB (NF-ĸB), a transcription factor necessary for either iNOS or COX-2 induction. Cyclolinteinone also blocked disappearance of IĸB-α from cytosolic fraction and nuclear translocation of NF-ĸB subunits p50 and p65. These results show that cyclolinteinone down-regulates iNOS and COX-2 protein expression by inhibiting NF-ĸB activation and suggest that it may represent a novel anti-inflammatory compound capable of controlling the excessive production of prostaglandins and nitric oxide occurring in several inflammatory diseases.
8
VAN PHI, Loc. "Transcriptional activation of the chicken lysozyme gene by NF-κ Bp65 (RelA) and c-Rel, but not by NF-κ Bp50." Biochemical Journal 313, no. 1 (January 1, 1996): 39–44. http://dx.doi.org/10.1042/bj3130039.
Full textAbstract:
The lysozyme gene is expressed at a low level in myeloblasts and is progressively activated to constitutively high expression in mature macrophages. The binding activity of the newly defined NF-ĸB/Rel family of transcription factors increases during the terminal differentiation of macrophages. In this study, I show that NF-ĸB/Rel-like proteins bind to the nuclear factor kappa B (ĸB)-like sequence of the lysozyme promoter. These binding activities were induced by treatment of HD11 cells with lipopolysaccharide. Immunomobility shift assays show that c-Rel is possibly a factor in the complexes that bind to the ĸB-like sequence lysĸB. Binding activity to one of the protein complexes seems to be regulated by phosphorylation. In fact, overexpression of p65 and c-Rel stimulates expression of the chloramphenicol acetyltransferase gene controlled by the lysozyme promoter. Furthermore, co-transfection experiments reveal that the ĸB-like sequence within the lysozyme promoter mediates the transactivation by p65 and c-Rel. These results indicate that the p65 and c-Rel could be components of the protein complexes that bind to the ĸB-like sequence and this binding could contribute to the progressively activated expression of the lysozyme gene during the terminal differentiation of macrophages.
9
Mörs, Katharina, Jason-Alexander Hörauf, Shinwan Kany, Nils Wagner, Ramona Sturm, Mathias Woschek, Mario Perl, Ingo Marzi, and Borna Relja. "Ethanol Decreases Inflammatory Response in Human Lung Epithelial Cells by Inhibiting the Canonical NF-kB-Pathway." Cellular Physiology and Biochemistry 43, no. 1 (2017): 17–30. http://dx.doi.org/10.1159/000480313.
Full textAbstract:
Background/Aims: Alcohol (ethanol, EtOH) as significant contributor to traumatic injury is linked to suppressed inflammatory response, thereby influencing clinical outcomes. Alcohol-induced immune-suppression during acute inflammation (trauma) was linked to nuclear factor-kappaB (NF-ĸB). Here, we analyzed alcohol`s effects and mechanisms underlying its influence on NF-ĸB-signaling during acute inflammation in human lung epithelial cells. Methods: A549-cells were stimulated with interleukin (IL)-1β, or sera from trauma patients (TP) or healthy volunteers, with positive/negative blood alcohol concentrations (BAC), and subsequently exposed to EtOH (170 Mm, 1h). IL-6-release and neutrophil adhesion to A549 were analyzed. Specific siRNA-NIK mediated downregulation of non-canonical, and IKK-NBD-inhibition of canonical NF-ĸB signaling were performed. Nuclear levels of activated p50 and p52 NF-ĸB-subunits were detected using TransAm ELISA. Results: Both stimuli significantly induced IL-6-release (39.79±4.70 vs. 0.58±0.8 pg/ml) and neutrophil adhesion (132.30±8.80 vs. 100% control, p<0.05) to A549-cells. EtOH significantly decreased IL-6-release (22.90±5.40, p<0.05) and neutrophil adherence vs. controls (105.40±14.5%, p<0.05). IL-1β-induced significant activation of canonical/p50 and non-canonical/p52 pathways. EtOH significantly reduced p50 (34.90±23.70 vs. 197.70±36.43, p<0.05) not p52 activation. Inhibition of canonical pathway was further increased by EtOH (less p50-activation), while p52 remained unaltered. Inhibition of non-canonical pathway was unchanged by EtOH. Conclusion: Here, alcohol`s anti-inflammatory effects are mediated via decreasing nuclear levels of activated p50-subunit and canonical NF-ĸB signaling pathway.
10
Rahaju, Pudji, Ayunita Tri Wirattami, Ferry Sandra, Steffi Kurniawan, Khairun Nisa, Soehartono Soehartono, Edi Handoko, et al. "A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma." Indonesian Biomedical Journal 13, no. 4 (December 31, 2021): 350–4. http://dx.doi.org/10.18585/inabj.v13i4.1580.
Full textAbstract:
BACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-2
11
Świerszcz, Łukasz, Anna Roszkowska, Kinga Ruszel, Marta Wójciak-Czuła, Andrzej Borzęcki, Barbara Nieradko-Iwanicka, and Piotr Siermontowski. "Effect of Lambda-Cyhalothrin - An Insecticide from the Group of Synthetic Pyrethroids - on the Concentrations of NF-ĸB and VEGFR2 in the Liver of Albino Swiss Mice as Markers of its Damage." Polish Hyperbaric Research 75, no. 2 (June 1, 2021): 57–68. http://dx.doi.org/10.2478/phr-2021-0011.
Full textAbstract:
Abstract Background: Lambda-cyhalothrin (LCH) is a one of the type II synthetic pyrethroids which is widely used in veterinary medicine and in agriculture to protect crops from pest insects. In previous studies, there are few reports about the influence of pyrethroids on the liver and its damage. Analyzing numerous publications, nuclear factor-ĸB (NF-ĸB) and vascular endothelial growth factor 2 (VEGFR2) seem to be sensitive indicators of microdamages occurring at the cellular level in the liver. The aim of the study was to investigate the effect of subacute poisoning with LCH on the concentration of NFĸB and VEGFR2 in the livers. Methods: The experiment was carried on 32 Albino Swiss mice (16 females and 16 males). The animals were divided into 4 groups. Controls received canola oil, the rest received LCH orally in oil at a dose of 2 mg/kg bw for 7 days. The NF-ĸB and VEGFR2 were mesuredin mice livers with ELISA kits. Results: The mean NF-ĸB concektration in control femals’ livers was 3.27ng/mL and after LCH it was 6.12ng/mL (p<0.05). In control males it was 5.49ng/mL and it did not significantly differ after LCH when it was 5.27ng/mL. The mean VEGFR2 in control females was 84.28ng/mL and after LCH it was 173.81ng/mL (p<0.05). In control males it was 170.61ng/mL and after LCH 170.06ng/mL. Conclusion:The NF-ĸB and VEGFR2 can be used as markers of liver damage after subacute poisoning with LCH on female mice. Females are more sensitive to LCH than males.
12
Dijkstra, Johannes M., and David B. Alexander. "The “NF-ĸB interacting long noncoding RNA” (NKILA) transcript is antisense to cancer-associated gene PMEPA1." F1000Research 4 (April 22, 2015): 96. http://dx.doi.org/10.12688/f1000research.6400.1.
Full textAbstract:
This correspondence concerns a recent publication inCancer Cellby Liu et al.1 who analyzed a long noncoding RNA (lncRNA) that they designated “NKILA”. Liu et al. found thatNKILA(1) is upregulated by immunostimulants, (2) has a promoter with an NF-ĸB binding motif, (3) can bind to the p65 protein of the NF-ĸB transcription factor and then interfere with phosphorylation of IĸBα, and (4) negatively affects functions that involve NF-ĸB pathways. And, importantly, they found that (5) lowNKILAexpression in breast cancers is associated with poor patient prognosis. However, they entirely failed to mentionPMEPA1, a gene which runs antisense toNKILA, and the expression of which is associated with several tumors and which encodes a protein that participates in immune pathways.ThePMEPA1locus, including its promoter region, which Liu et al.1only discuss in regard toNKILA, is highly conserved through evolution. Our impression is thatNKILAemerged only later in evolution, possibly as an additional means ofPMEPA1regulation. Liu et al., however, only consider direct binding betweenNKILAand NF-ĸB as the mechanism for theirin vivoobservations ofNKILAfunction, but do not provide solid evidence for their model. Ifin vivoobservations by Liu et al. could be explained byNKILAregulation ofPMEPA1, it would contribute to the establishment ofPMEPA1as an important topic of cancer research. We feel that the herein presented discussion is necessary for a correct interpretation of the Liu et al. article.
13
XIA, Chulin, Jiangting HU, Brian KETTERER, and John B. TAYLOR. "The organization of the human GSTP1-1 gene promoter and its response to retinoic acid and cellular redox status." Biochemical Journal 313, no. 1 (January 1, 1996): 155–61. http://dx.doi.org/10.1042/bj3130155.
Full textAbstract:
High levels of expression of GSTP1-1 are associated with cell proliferation, embryogenesis and malignancy. Given the role of glutathione S-transferase (GST) in detoxication, it is possible that GSTP1-1 evolved specifically to protect proliferating cells and share regulatory mechanisms with other cellular genes which are involved in cell division and tumorigenesis. We have previously shown that the expression of GSTP1 is suppressed by retinoic acid (RA) in the presence of the retinoic acid receptor (RAR) as a result of decreased transcription from its promoter. Through deletion analysis, we show here that the RA-RAR-dependent repression is mediated by the region -73 to +8. Further mutation analysis of this region indicates that the DNA sequence required for RA-RAR-dependent repression co-localizes with a consensus activator protein-1 (AP1) site essential for the promoter activity. The degree of repression correlates with the residual activity of the AP1 site. There are two adjacent G/C boxes. The one immediately downstream from the AP1 site is not essential for the promoter activity, but mutation of the second, further downstream, impairs the promoter. On the other hand, mutation of either of these two G/C boxes has little effect on RA-RAR suppression. We also show that the expression of GSTP1 is regulated by the redox status of the cell. Using the chloramphenicol acetyltransferase assay system, we have demonstrated that treatment with H2O2 induced transcription from the promoter and that this effect can be blocked by pre-incubation with N-acetylcysteine (NAC). It was shown that the induction by H2O2 is mediated by trans-acting factor NF-ĸB (nuclear factor ĸB), via a putative NF-ĸB site, ‘GGGACCCTCC’, located from -96 to -86. Co-transfection with an NF-ĸB (p65) expression construct increased the promoter activity, an effect which could be blocked by co-transfection with an IĸB (MAD-3) expression construct. Deletion of the NF-ĸB site abolished the effect of both H2O2 and co-transfection of NF-ĸB. Interestingly, NAC is also an inducer for GSTP1. The effect of NAC was shown to be mediated largely by the AP1 site, since mutation of this site abolished the induction by NAC.
14
Dahlke, Eileen, Toni Engmann, Yaman Anan, Robert Häsler, Giovanni Solinas, and Franziska Theilig. "Tubular IKKβ Deletion Alleviates Acute Ischemic Kidney Injury and Facilitates Tissue Regeneration." International Journal of Molecular Sciences 23, no. 17 (September 5, 2022): 10199. http://dx.doi.org/10.3390/ijms231710199.
Full textAbstract:
Acute kidney injury (AKI) is a common renal injury leading to relevant morbidity and mortality worldwide. Most of the clinical cases of AKI are caused by ischemia reperfusion (I/R) injury with renal ischemia injury followed by reperfusion injury and activation of the innate immune response converging to NF-ĸB pathway induction. Despite the clear role of NF-ĸB in inflammation, it has recently been acknowledged that NF-ĸB may impact other cell functions. To identify NF-ĸB function with respect to metabolism, vascular function and oxidative stress after I/R injury and to decipher in detail the underlying mechanism, we generated a transgenic mouse model with targeted deletion of IKKβ along the tubule and applied I/R injury followed by its analysis after 2 and 14 days after I/R injury. Tubular IKKβ deletion ameliorated renal function and reduced tissue damage. RNAseq data together with immunohistochemical, biochemical and morphometric analysis demonstrated an ameliorated vascular organization and mRNA expression profile for increased angiogenesis in mice with tubular IKKβ deletion at 2 days after I/R injury. RNAseq and protein analysis indicate an ameliorated metabolism, oxidative species handling and timely-adapted cell proliferation and apoptosis as well as reduced fibrosis in mice with tubular IKKβ deletion at 14 days after I/R injury. In conclusion, mice with tubular IKKβ deletion upon I/R injury display improved renal function and reduced tissue damage and fibrosis in association with improved vascularization, metabolism, reactive species disposal and fine-tuned cell proliferation.
15
Wei, Liming, Boqun Cao, Chen Jia, Rui Zhang, Yuting Liu, and Yujun Qiao. "Protective effect of Wuling mycelia, alone and in combination with valproic acid, on pentylenetetrazolinduced epilepsy in rats." Tropical Journal of Pharmaceutical Research 20, no. 1 (March 19, 2021): 135–43. http://dx.doi.org/10.4314/tjpr.v20i1.20.
Full textAbstract:
Purpose: To determine the inhibitory effects of Wuling mycelia, alone and in combination with valproic acid (VPA) on pentylenetetrazol (PTZ)-induced epileptic seizure in rats, and their protective effects on cognitive impairment.Methods: Sprague-Dawley rats were randomly divided into five groups: control (sham), model, Wuling mycelia, VPA and combination groups. Rats in Wuling mycelia group were given oral Wuling mycelia alone at a dose of 594 mg/kg, while those in VPA group were given oral VPA alone at a dose of 189 mg/kg. In the combination group, rats received oral VPA at a dose of 189 mg/kg co-administered with Wuling mycelia at a dose of 594 mg/kg. One hour after the treatments, the control group was injected with physiological saline intraperitoneally, while the other four groups were injected with PTZ solution once a day for 28 days. Subsequently, seizure intensity, cognitive impairment, neuronal loss and hippocampal expressions of IL-1β, NF-ĸB/p65 and TLR4 were determine in all groups.Results: Combined use of Wuling mycelium and VPA significantly reduced the frequency and the grade of seizures (p <0.01), and also decreased the degree of cognitive impairment (p <0.05). There were marked increases in neuronal damage and hippocampal expression levels of NF-ĸB/p65, TLR4 and IL1β (inflammatory cytokines) in the model group (p < 0.05). However, these changes were reversed in the combination treatment group (p < 0.05).Conclusion: Wuling mycelia is a potentially effective adjunct drug for the treatment of refractory epilepsy. The underlying mechanism might involve downregulations of NF-ĸB/p65, TLR4 and IL-1β.
Keywords: Wuling mycelia, Refractory epilepsy, Seizure, Traditional Chinese medicine, Hippocampal area, HMGB1/TLR4/NF-κB signalling pathway, IL-1β, NF-ĸB/p65, TLR4
16
de Jesus, Ma Sheila M., Allan Patrick G. Macabeo, John Donnie A. Ramos, Von Novi O. de Leon, Kaori Asamitsu, and Takashi Okamoto. "Voacanga globosa Spirobisindole Alkaloids Exert Antiviral Activity in HIV Latently Infected Cell Lines by Targeting the NF-kB Cascade: In Vitro and In Silico Investigations." Molecules 27, no. 3 (February 5, 2022): 1078. http://dx.doi.org/10.3390/molecules27031078.
Full textAbstract:
Since the efficiency in the transcription of the HIV genome contributes to the success of viral replication and infectivity, we investigated the downregulating effects of the spirobisindole alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) from the endemic Philippine medicinal plant, Voacanga globosa, during HIV gene transcription. Alkaloids 1–3 were explored for their inhibitory activity on TNF-α-induced viral replication in two latently HIV-infected cell lines, OM10.1 and J-Lat. The induction of HIV replication from OM10.1 and J-Lat cells elicited by TNF-α was blocked by globospiramine (1) within noncytotoxic concentrations. Furthermore, globospiramine (1) was found to target the NF-ĸB activation cascade in a dose-dependent manner when the transcriptional step at which inhibitory activity is exerted was examined in TNF-α-induced 293 human cells using transient reporter (luciferase) gene expression systems (HIV LTR-luc, ĸB-luc, and mutant ĸB-luc). Interrogation through molecular docking against the NF-ĸB p50/p65 heterodimer and target sites of the subunits comprising the IKK complex revealed high binding affinities of globospiramine (1) against the S281 pocket of the p65 subunit (BE = −9.2 kcal/mol) and the IKKα activation loop (BE = −9.1 kcal/mol). These findings suggest globospiramine (1) as a molecular inspiration to discover new alkaloid-based anti-HIV derivatives.
17
Kravtsova-Ivantsiv, Yelena, Gilad Goldhirsh, Alexandra Ivantsiv, Ofer Ben Itzhak, Yong Tae Kwon, Eli Pikarsky, and Aaron Ciechanover. "Excess of the NF-ĸB p50 subunit generated by the ubiquitin ligase KPC1 suppresses tumors via PD-L1– and chemokines-mediated mechanisms." Proceedings of the National Academy of Sciences 117, no. 47 (November 9, 2020): 29823–31. http://dx.doi.org/10.1073/pnas.2019604117.
Full textAbstract:
Nuclear factor–ĸB (NF-ĸB) transcription factor is a family of essential regulators of the immune response and cell proliferation and transformation. A typical factor is a heterodimer made of either p50 or p52, which are limited processing products of either p105 or p100, respectively, and a member of the Rel family of proteins, typically p65. The transcriptional program of NF-ĸB is tightly regulated by the composition of the dimers. In our previous work, we demonstrated that the ubiquitin ligase KPC1 is involved in ubiquitination and proteasomal processing of p105 to generate p50. Its overexpression and the resulting high level of p50 stimulates transcription of a broad array of tumor suppressors. Here we demonstrate that additional mechanisms are involved in the p50-mediated tumor-suppressive effect. p50 down-regulates expression of a major immune checkpoint inhibitor, the programmed cell death-ligand 1 (PD-L1), both in cells and in tumors. Importantly, the suppression is abrogated by overexpression of p65. This highlights the importance of the cellular quantities of the two different subunits of NF-ĸB which determine the composition of the dimer. While the putative p50 homodimer is tumor-suppressive, the “canonical” p50p65 heterodimer is oncogenic. We found that an additional mechanism is involved in the tumor-suppressive phenomenon: p50 up-regulates expression of the proinflammatory chemokines CCL3, CCL4, and CCL5, which in turn recruit into the tumors active natural killer (NK) cells and macrophages. Overall, p50 acts as a strong tumor suppressor via multiple mechanisms, including overexpression of tumor suppressors and modulation of the tumor microenvironment by recruiting active immune cells.
18
Wang, Gaolin, Bo Sun, Xiangpeng Meng, and Bin Ge. "Effect of Bone Marrow Stromal Stem Cells (BMSCs) Therapy on the Expression of Sodium Channel, Voltage-Gated, Type I, Alpha Subunit (SCN1A) in Temporal Lobe Epilepsy and Its Mechanism." Journal of Biomaterials and Tissue Engineering 11, no. 8 (August 1, 2021): 1565–70. http://dx.doi.org/10.1166/jbt.2021.2704.
Full textAbstract:
SCN1A gene plays an indispensable role in several diseases. Bone marrow stromal stem cells (BMSCs) therapy is a potential target for treating epilepsy, but its therapeutic effect and mechanism is unclear. Our study aims to investigate the mechanism by how BMSCs affect epilepsy. Wistar rats were assigned into control group, model group (pilocarpine-induced TLE model), and BMSCs group followed by measuring the latency of field excitatory postsynaptic potential, pathological changes, SCN1A level by Real time PCR, NF-ĸB and TLR4 expression by Western blot, and HGMB1, TLR4, IL-1β and IL-6 secretion by ELISA. In model group, the incubation period of postsynaptic potential generation was significantly shortened and SCN1A level was significantly decreased, along with increased NF-ĸB expression and secretion of HMGB1, TLR-4, IL-1β and IL-6 (P < 0.05). After BMSCs treatment, the incubation period of postsynaptic potentials can be significantly prolonged and SCN1A was significantly upregulated, with ameliorated epilepsy injury and reduced secretion of related factors (P <0.05). Pilocarpine-induced TLE can reduce SCN1A expression and BMSCs therapy can up-regulate SCN1A expression by regulating NF-ĸB/HGMB1/TLR4 signaling pathway, thereby protecting neurons, reducing pathological damage, and ameliorating the development of epilepsy.
19
Chang, Tsui, Lin, Hou, Feng, and Juang. "Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo." Cancers 11, no. 10 (October 2, 2019): 1486. http://dx.doi.org/10.3390/cancers11101486.
Full textAbstract:
: Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.
20
Zulkapli, Rahayu, Suhaila Abd Muid, Seok Mui Wang, and Hapizah Nawawi. "PCSK9 Inhibitors Reduce PCSK9 and Early Atherogenic Biomarkers in Stimulated Human Coronary Artery Endothelial Cells." International Journal of Molecular Sciences 24, no. 6 (March 7, 2023): 5098. http://dx.doi.org/10.3390/ijms24065098.
Full textAbstract:
Despite reports on the efficacy of proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors as a potent lipid-lowering agent in various large-scale clinical trials, the anti-atherogenic properties of PCSK9 inhibitors in reducing PCSK9 and atherogenesis biomarkers via the NF-ĸB and eNOS pathway has yet to be established. This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). HCAEC were stimulated with lipopolysaccharides (LPS) and incubated with evolocumab and alirocumab. The protein and gene expression of PCSK9, interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-ĸB) p65, and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. The binding of U937 monocytes to endothelial cell capacity was measured by the Rose Bengal method. The anti-atherogenic effects of evolocumab and alirocumab were contributed to by the downregulation of PCSK9, early atherogenesis biomarkers, and the significant inhibition of monocyte adhesion to the endothelial cells via the NF-ĸB and eNOS pathways. These suggest the beyond cholesterol-lowering beneficial effects of PCSK9 inhibitors in impeding atherogenesis during the initial phase of atherosclerotic plaque development, hence their potential role in preventing atherosclerosis-related complications.
21
Handono, Kusworini, Tri W. I. Dantara, Elvira S. Dewi, Mirza Z. Pratama, and Nurdiana Nurdiana. "Bryophyllum pinnatum leaves ethanol extract inhibit maturation and promote apoptosis of systemic lupus erythematosus BALB/c mice B cells." Medical Journal of Indonesia 26, no. 4 (February 14, 2018): 253–60. http://dx.doi.org/10.13181/mji.v26i4.1899.
Full textAbstract:
Background: B cells play a key role in systemic lupus erythematosus (SLE). Targeting B cells as SLE therapy is a plausible approach. This study investigated the potential effects of Bryophyllum pinnatum leaves with ethanol extract in decreasing percentages of maturation, increasing percentages of apoptosis, and decreasing NF-κB p65 expressions of SLE BALB/c mice B cells.Methods: Culturing B cells from pristane induced SLE BALB/c mice’s spleen will resulted in this in vitro study. B cells were activated by BAFF, LPS, IL-4, and anti-CD40 yielding CD19+ >80%. B cells were cultured by adding those stimulants with and without B. pinnatum leaves (0, 0.02, 0.1, or 0.5 µg/ml) for 72 hours at 37°C. Flow cytometry was performed to determine The Percentages of maturation (CD19+CD38+) and apoptosis (Annexin V+PI+) of B cells. Further analysis to determine the expressions of transcription factor of maturation and apoptosis of B cells, NF-ĸB p65, were performed using immunocytochemistry. Data were analyzed using SPSS version 22.Results: Flow cytometry assay showed significant decrease in percentages of maturation of B cells in all doses and significant increase in percentage of apoptosis of B cells in dose 0.5 µg/ml. Immunocytochemistry results showed significant decrease expressions of NF-ĸB p65 in all doses. Percentages of maturation, apoptosis, and expressions of NF-ĸB p65 of B cells were significantly correlated.Conclusion: This in vitro study revealed that B. pinnatum leaves with ethanol extract decreased the percentages of maturation, increased the percentage of apoptosis, and decreased NF-κB p65 expressions of SLE BALB/c mice B cells significantly.
22
Nešić, Andrijana, Milena Čavić, Milica Popović, Milena Zlatanova, Raymond Pieters, Joost Smit, and Marija Gavrović-Jankulović. "The Kiwifruit Allergen Act d 1 Activates NF-κB Signaling and Affects mRNA Expression of TJ Proteins and Innate Pro-Allergenic Cytokines." Biomolecules 9, no. 12 (December 2, 2019): 816. http://dx.doi.org/10.3390/biom9120816.
Full textAbstract:
Impairment of the intestinal barrier is one of the key events in the initiation of the sensitization process in food allergy. The aim of this study was to explore the effects of kiwifruit allergen Act d 1 on intestinal permeability and tight junction protein (TJP) gene expression in vivo and to explore its potential to activate the NF-ĸB signaling pathway and to regulate expression of epithelial pro-allergenic cytokines. Influences of Act d 1 on TJP gene expression and pro-allergenic cytokines in the mouse intestine was analyzed by qPCR upon allergen administration by oral gavage. The effect on the in vivo intestinal permeability was assessed in ELISA by measuring the translocation of β-lactoglobulin (BLG) into circulation. The capacity of Act d 1 to activate the NF-ĸB pathway was tested in HEK293 cells by fluorescent microscopy and flow cytometry. Administration of Actinidin (Act d 1) increased intestinal permeability to the BLG. This was accompanied by changes in gene expression of TJP mRNA and pro-allergenic cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) compared to the control. Act d 1 reduced TEER of the HEK293 monolayer, was positive in an NF-ĸB-reporter HEK293 cell assay, and induced secretion of TSLP. These findings shed more light on the molecular events in the sensitization process of kiwifruit but possibly also of other protease food allergens.
23
Collins, Patricia E., Domenico Somma, David Kerrigan, Felicity Herrington, Karen Keeshan, Robert J. B. Nibbs, and Ruaidhrí J. Carmody. "The IκB-protein BCL-3 controls Toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus." Proceedings of the National Academy of Sciences 116, no. 51 (November 26, 2019): 25828–38. http://dx.doi.org/10.1073/pnas.1900408116.
Full textAbstract:
Proinflammatory responses induced by Toll-like receptors (TLRs) are dependent on the activation of the NF-ĸB and mitogen-activated protein kinase (MAPK) pathways, which coordinate the transcription and synthesis of proinflammatory cytokines. We demonstrate that BCL-3, a nuclear IĸB protein that regulates NF-ĸB, also controls TLR-induced MAPK activity by regulating the stability of the TPL-2 kinase. TPL-2 is essential for MAPK activation by TLR ligands, and the rapid proteasomal degradation of active TPL-2 is a critical mechanism limiting TLR-induced MAPK activity. We reveal that TPL-2 is a nucleocytoplasmic shuttling protein and identify the nucleus as the primary site for TPL-2 degradation. BCL-3 interacts with TPL-2 and promotes its degradation by promoting its nuclear localization. As a consequence,Bcl3−/−macrophages have increased TPL-2 stability following TLR stimulation, leading to increased MAPK activity and MAPK-dependent responses. Moreover, BCL-3–mediated regulation of TPL-2 stability sets the MAPK activation threshold and determines the amount of TLR ligand required to initiate the production of inflammatory cytokines. Thus, the nucleus is a key site in the regulation of TLR-induced MAPK activity. BCL-3 links control of the MAPK and NF-ĸB pathways in the nucleus, and BCL-3–mediated TPL-2 regulation impacts on the cellular decision to initiate proinflammatory cytokine production in response to TLR activation.
24
Budiutari, Ni Nyoman, Yoes Prijatna Dachlan, and Jusak Nugraha. "OVERVIEW OF NUCLEAR FACTOR-KB (NF-KB) AND NON-STRUCTURAL PROTEIN 1 (NS1) IN PATIENTS WITH DENGUE FEVER IN PREMIER HOSPITAL, SURABAYA." Indonesian Journal of Tropical and Infectious Disease 7, no. 5 (May 22, 2019): 109. http://dx.doi.org/10.20473/ijtid.v7i5.9955.
Full textAbstract:
Dengue fever (DF) is an acute viral fever caused by RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DF is also called viral arthropod-borne disease and is accompanied by headaches, joint and muscle pain. The main target of dengue infection is macrophages or monocytes and dendritic cells (DC). Infected DC is caused the viral replication and the endocytosis into endosomal, easier, thus inducing the activation of NF-ĸB transcription factor to produce proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-1 (IL-1), IL-6, IL-12 and chemokine. NF-kB is one of the transcription factors involved in the regulation of the expression of various cytokines, chemokines and anti/pro-apoptotic proteins during infection and act as indicator of disease severity. Infected DC cells are secreted NS1 protein which is the co-factor needed for viral replication and can be detected in the first eight days. The level will be higher in the initial phase of fever. The purpose of this study was to analyze the description of NF-kB and NS1 levels in the serum of patients with dengue fever through observational analytic studies through a cross-sectional approach. This study was done on 40 patients with dengue fever and 10 healthies people as negative controls. NS1 was analyzed in serum of Panbio rapid test and NF-kB level were measured by sandwich ELISA. The results are showed positive and negative NS1 results in dengue fever patients. The average NF-kB serum level in dengue fever patients was found to be higher than the control. NF-ĸB level in negative NS1 was higher than the NS1 positive group. It is showed that NS1 is detected both in the acute phase. The detection of NF-ĸB is showed the involvement of transcription factors in the development of dengue virus infection and has a protective role for host cells.
25
Qiang, Zhe, Wenli Yu, and Yonghao Yu. "Design and Development of Novel 1,3,5-Triazine-Procaine Derivatives as Protective Agent against Myocardial Ischemia/Reperfusion Injury via Inhibitor of Nuclear Factor-κB." Pharmacology 104, no. 3-4 (2019): 126–38. http://dx.doi.org/10.1159/000500702.
Full textAbstract:
The aim of the present study was to determine the protective effect of novel 1,3,5-triazine-procaine derivatives against myocardial ischemia/reperfusion (I/R) injury. Initially, the experiment has been started by the synthesis of procaine, which later got substituted with diverse 1,3,5-triazine derivatives to furnish the final compounds. The target compounds were tested for nuclear factor-κB (NF-κB) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The antioxidant activity of most potent compound 9i was investigated using hydroxyl radical, DPPH, and superoxide anion scavenging assay. Compound 9i was further evaluated for protective effect against myocardial I/R injury on the basis numerous parameters, for example, hemodynamic parameters (left ventricular developed pressure [LVDP], ±dp/dtmax, coronary flow [CF], and heart rate [HR]), myocardial enzymes (creatine kinase and lactate dehydrogenase), thiobarbituric acid reactive substance (TBARS), oxidative stress (super oxide dismutase [SOD], catalase [CAT], glutathione [GSH], and glutathione peroxidise [GPx]), histopathology, western blots analysis for B-cell lymphoma 2 (Bcl-2), Bcl-2-associated x protein (Bax), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and NF-κB in cardiac tissues. Compounds showed significant inhibition of NF-ĸB transcriptional activity in LPS-stimulated RAW264.7 cells, revealing compound 9i as a most potent derivative. In vitro results showed efficient reduction of reduced hydroxyl radical, DPPH, and superoxide anion by 9i. The level LVDP, ±dp/dtmax, CF, HR, TBARS, SOD, CAT, GSH, GPx, and damaged cardiac histopathology were completely restored to normal in 9i-treated group, as compared to I/R group. In western blot analysis, the expression of Bax, LOX-1, and NF-ĸB was found to be decreased, while the level of Bcl-2 was found to be increased in 9i-treated group. The procaine-1,3,5-triazine derivatives showed significant cardioprotective action via inhibition of NF-ĸB.
26
Schmitz, M. Lienhard, Susanne Bacher, and Oliver Dienz. "NF‐ĸB activation pathways induced by T cell costimulation." FASEB Journal 17, no. 15 (December 2003): 2187–93. http://dx.doi.org/10.1096/fj.02-1100rev.
Full text
27
Torres, Luis, Eva Serna, Ana Bosch, Rosa Zaragozá, Concha García, Vicente J. Miralles, Juan Sandoval, Juan R. Viña, and Elena R. García-Trevijano. "NF-ĸB as Node for Signal Amplification During Weaning." Cellular Physiology and Biochemistry 28, no. 5 (2011): 833–46. http://dx.doi.org/10.1159/000335797.
Full text
28
AlQasrawi, Dania, Ebraheem Naser, and Saleh A. Naser. "Nicotine Increases Macrophage Survival through α7nAChR/NF-κB Pathway in Mycobacterium avium paratuberculosis Infection." Microorganisms 9, no. 5 (May 18, 2021): 1086. http://dx.doi.org/10.3390/microorganisms9051086.
Full textAbstract:
Recently, we reported that nicotine plays a role in the failure of the macrophage in the clearance of Mycobacterium avium subspecies paratuberculosis (MAP) during infection in Crohn’s disease smokers. We also demonstrated that nicotine enhances macrophages cellular survival during MAP infection. Blocking α7 nicotinic acetylcholine receptor (α7nAChR) with the pharmacological antagonist—mecamylamine—subverted the anti-inflammatory effect of nicotine in macrophages. Yet, it is still unknown how α7nAChR is involved in the modulation of the macrophage response during MAP infection. Here, we studied the mechanistic role of nicotine-α7nAChR interaction in modulating NF-ĸB survival pathway, autophagy, and effect on cathelicidin production in MAP-infected macrophages using THP-1 cell lines. Our results showed that nicotine upregulated α7nAChR expression by 5-folds during MAP infection compared to controls. Bcl-2 expression was also significantly increased after nicotine exposure. Moreover, Nicotine inhibited autophagosome formation whereas infection with MAP in absence of nicotine has significantly increased LC-3b in macrophages. Nicotine also further upregulated NF-ĸB subunits expression including Rel-B and p100, and increased nuclear translocation of p52 protein. We also discovered that cathelicidin production was significantly suppressed in MAP-infected macrophages, treatment with nicotine showed no effect. Overall, the study provides new insight toward understanding the cellular role of nicotine through α7nAChR/NF-ĸB p100/p52 signaling pathway in inducing anti-apoptosis and macrophage survival during MAP infection in Crohn’s disease smokers.
29
Zhang, Xiao, Shaurita D. Hutchins, Bruce E. Blough, and Eric J. Vallender. "In Vitro Effects of Ligand Bias on Primate Mu Opioid Receptor Downstream Signaling." International Journal of Molecular Sciences 21, no. 11 (June 3, 2020): 3999. http://dx.doi.org/10.3390/ijms21113999.
Full textAbstract:
Interest has emerged in biased agonists at the mu opioid receptor (MOR) as a possible means for maintaining potent analgesis with reduced side effect profiles. While approaches measuring in vitro biased agonism are used in the development of these compounds, their therapeutic utility will ultimately be determined by in vivo functional effects. Nonhuman primates (NHPs) are the most translational model for evaluating the behavioral effects of candidate medications, but biased signaling of these drugs at NHP MOR receptors has been unstudied. The goal of the current work was to characterize MOR ligand bias in rhesus macaques, focusing on agonists that have previously been reported to show different patterns of biased agonism in rodents and humans. Downstream signaling pathways that responded to MOR activation were identified using a luciferase reporter array. Concentration-response curves for specific pathways (cAMP, NF-ĸB, MAPK/JNK) were generated using six agonists previously reported to differ in terms of signaling bias at rodent and human MORs. Using DAMGO as a reference ligand, relative cAMP, NF-ĸB and MAPK/JNK signaling by morphine, endomorphin-1, and TRV130 were found to be comparable between species. Further, the bias patterns of across ligands for NF-ĸB and MAPK/JNK were largely similar between species. There was a high degree of concordance between rhesus macaque and human MOR receptor signaling bias for all agonists tested, further demonstrating their utility for future translational behavioral studies.
30
Ielciu, Irina, Gabriela Adriana Filip, Ilioara Oniga, Neli-Kinga Olah, Ioana Bâldea, Diana Olteanu, Ramona Flavia Burtescu, et al. "Oxidative Stress and DNA Lesion Reduction of a Polyphenolic Enriched Extract of Thymus marschallianus Willd. in Endothelial Vascular Cells Exposed to Hyperglycemia." Plants 10, no. 12 (December 18, 2021): 2810. http://dx.doi.org/10.3390/plants10122810.
Full textAbstract:
The present study aimed to compare two polyphenolic-enriched extracts obtained from the Thymus marschallianus Willd. (Lamiaceae) species, harvested from culture (TMCE in doses of 0.66 μg GAE/mL and 0.066 μg GAE/mL) and from spontaneous flora (TMSE in doses of 0.94 μg GAE/mL and 0.094 μg GAE/mL) by assessing their biological effects on human umbilical vein endothelial cells (HUVECs) exposed to normoglycemic (137 mmol/L glucose) and hyperglycemic conditions (200 mmol/L glucose). Extracts were obtained by solid phase extraction (SPE) and analyzed by chromatographical (HPLC-DAD) and spectrophotometrical methods. Their effects on hyperglycemia were evaluated by the quantification of oxidative stress and NF-ĸB, pNF-ĸB, HIF-1α, and γ-H2AX expressions. The HPLC-DAD analysis highlighted significant amounts of rosmarinic acid (ranging between 0.18 and 1.81 mg/g dry extract), luteolin (ranging between 2.04 and 17.71 mg/g dry extract), kaempferol (ranging between 1.85 and 7.39 mg/g dry extract), and apigenin (ranging between 4.97 and 65.67 mg/g dry extract). Exposure to hyperglycemia induced oxidative stress and the activation of NF-ĸ increased the expression of HIF-1α and produced DNA lesions. The polyphenolic-enriched extracts proved a significant reduction of oxidative stress and γ-H2AX formation and improved the expression of HIF-1α, suggesting their protective role on endothelial cells in hyperglycemia. The tested extracts reduced the total NF-ĸB expression and diminished its activation in hyperglycemic conditions. The obtained results bring evidence for the use of the polyphenolic-enriched extracts of T. marschallianus as adjuvants in hyperglycemia.
31
Caetano-Silva, Soraia, Bigboy H. Simbi, Neil Marr, Andrew Hibbert, Steve P. Allen, and Andrew A. Pitsillides. "Restraint upon Embryonic Metatarsal Ex Vivo Growth by Hydrogel Reveals Interaction between Quasi-Static Load and the mTOR Pathway." International Journal of Molecular Sciences 22, no. 24 (December 8, 2021): 13220. http://dx.doi.org/10.3390/ijms222413220.
Full textAbstract:
Mechanical cues play a vital role in limb skeletal development, yet their influence and underpinning mechanisms in the regulation of endochondral ossification (EO) processes are incompletely defined. Furthermore, interactions between endochondral growth and mechanics and the mTOR/NF-ĸB pathways are yet to be explored. An appreciation of how mechanical cues regulate EO would also clearly be beneficial in the context of fracture healing and bone diseases, where these processes are recapitulated. The study herein addresses the hypothesis that the mTOR/NF-ĸB pathways interact with mechanics to control endochondral growth. To test this, murine embryonic metatarsals were incubated ex vivo in a hydrogel, allowing for the effects of quasi-static loading on longitudinal growth to be assessed. The results showed significant restriction of metatarsal growth under quasi-static loading during a 14-day period and concentration-dependent sensitivity to hydrogel-related restriction. This study also showed that hydrogel-treated metatarsals retain their viability and do not present with increased apoptosis. Metatarsals exhibited reversal of the growth-restriction when co-incubated with mTOR compounds, whilst it was found that these compounds showed no effects under basal culture conditions. Transcriptional changes linked to endochondral growth were assessed and downregulation of Col2 and Acan was observed in hydrogel-treated metatarsi at day 7. Furthermore, cell cycle analyses confirmed the presence of chondrocytes exhibiting S-G2/M arrest. These data indicate that quasi-static load provokes chondrocyte cell cycle arrest, which is partly overcome by mTOR, with a less marked interaction for NF-ĸB regulators.
32
Devi, J. Renuka, Nandhinidevi G, Bavanilatha M, Kavitha Bharathy T, Jameela Banu M, and Kanimozhi S. "THREE-DIMENSIONAL QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIPS MODELING STUDIES OF PHYTOCHEMICALS FROM BRASSICACEAE AS POTENT INHIBITORS AGAINST TUMOR INFLAMMATION." Asian Journal of Pharmaceutical and Clinical Research 10, no. 1 (January 1, 2016): 321. http://dx.doi.org/10.22159/ajpcr.2017.v10i1.15361.
Full textAbstract:
ABSTRACTObjective: The aim of this study was to develop a three-dimensional quantitative structure–activity relationships (3D-QSARs) model for studying theinteraction of different phytochemicals with nuclear factor kappa B (NF-ĸB) inducing kinase, a major regulator in tumor inflammation.Methods: Different phytochemicals (ligands) from Brassicaceae were selected and tested for Lipinski’s rule of five and further analyzed usinginteraction studies (docking) to identify the binding site in the target protein. Ligands with best fit were made to pass through ADMET filter, and thenontoxic ligands were selected based on the pIC50 values. Results: The 3D-QSARs of the ligands were designed using comparative molecular field analysis, and glucoraphanin was found to be stable and fitafter subjecting for molecular dynamics simulation with annealing studies.Conclusion: Thus, the model may be prospectively used in drug design to find possible inhibitors of NF-ĸB, which plays a key prominent role in cancerinflammation.Keywords: Three-dimensional quantitative structure–activity relationships, Brassica oleracea, Simulation, Annealing, Nuclear factor kappa B kinase.
33
Xu, Pengpeng, Huijuan Zhong, and Weili Zhao. "Additional Two Cycles of Rituximab Improves the Prognosis of Low-Risk NCCN-IPI Diffuse Large B-Cell Lymphoma Patients Responded to R-CHOP Regimen." Blood 126, no. 23 (December 3, 2015): 2733. http://dx.doi.org/10.1182/blood.v126.23.2733.2733.
Full textAbstract:
Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas with a relapse/refractory rate of 30-40% under the current standard Rituximab plus cyclophophamide, adrimycin, vincristine and prednisone (R-CHOP21) treatment. As mechanism of action, Rituximab can target the B-cell receptor (BCR) and NF-ĸB signaling pathways, of which activating gene mutations are most frequently identified in activated B-cell-like (ABC) subtype of DLBCL and associated with increased disease relapse of the patients. The aim of our study was to investigate the clinical efficacy of additional two cycles of Rituximab maintenance (RM) in DLBCL and its relation with mutational status involved in BCR/NF-ĸB cascade. Methods: We retrospectively analyzed a total of 534 de novo DLBCL patients after 6 cycles of R-CHOP21 regimen in our institution from December 1998 to December 2012. Among 413 patients achieved complete response (CR), 211 patients received additional 2 cycles of RM in a intent-to-treat manner and 202 patients underwent observation (OBS). The remaining 121 patients were primarly refractory to R-CHOP regimen. All the patients were classified according to IPI and NCCN-IPI as previously described. Immunohistochemistry for germinal center B-cell (GCB) or non-GCB subgroups were determined by Hans classification. The mutational status of BCR/NF-ĸB-associated genes (mainly as CD79A, CD79B, MYD88, and CARD11) were detected in tumor samples of 124 patients (48 cases, 43 cases and 33 cases in the RM, OBS and Refractory group, respectively). Results: No significant difference of clincial and biological characteristics were found between the RM and OBS group, including age, gender, Ann Arbor stage, ECOG score, number of extranodal involvements, serum lactic dehydrogenase level, B symptoms, IPI and NCCN-IPI risk group, and GCB/non-GCB ratio. With a median follow-up of 36.5 months, the 3-year progrssion free survival (PFS) was 79.9% and 73.6% (P=0.123), and the 3-year overall survival (OS) was 91.0% and 87.4% (P=0.149) in RM and OBS group, respectively. According to NCCN-IPI, remarkable improvement of 3-year PFS and OS was observed in low-risk patients of the RM group (100% and 100%), comparing with those of the OBS group (82.5% and 88.2%, P=0.003 and 0.027 respectively, Figure 1). Similarly, male patients with low-risk IPI could also benefit from additional 2 cycles of Rituximab with a 3-year PFS of 100% in RM vs 84.4% in OBS (P=0.006). Overall, BCR/NF-ĸB mutations were detected in 46/124 patients (37.1%), including 20/48 (41.7%), 13/43(30.2%) and 13/33 (39.4%) patients in RM, OBS and Refractory group, respectively. However, MYD88 mutations were more frequently observed in the Refractory group than in the RM/OBS group (18/33 vs 6/91, P<0.001, Table 1). Mutations are not prognostic indicators for PFS or OS in general, but interestingly, those mutation-bearing patients showed a tendency of improved disease prognosis in the RM group compared with that of the OBS group (3-year PFS 85.5% vs 70.0%, P=0.091, 3-year OS 94.7% vs 71.6%, P=0.059, Figure 2). Conclusion: Low-risk NCCI-IPI patients with DLBCL responded to R-CHOP regimen benefit from additional two cycles of RM. As a potential target of Rituximab, BCR/NF-ĸB-associated mutations reflected disease resistance to Rituximab. Whether prolonged administration of Rituximab could improve the prognosis of the patients with these mutations warrants further investigation. Table 1. The distribution of BCR/NF-κB-associated mutations in patients with DLBCL Mutated gene Refractory (N=33) CR (N=91) Additional 2R (N=48) Observation (N=43) P value CD79a 1 (3.0%) 0 (0%) 0 (0%) 0.595a CD79b 5 (15.1%) 10 (20.8%) 6 (13.9%) 0.750 a MYD88 18 (54.5%) 3 (6.0%) 3 (6.9%) <0.001b CARD11 1 (3.0%) 7 (14.0%) 4 (9.3%) 0.244a a: No significantly difference was found between Refractory group and CR group. b: Significantly difference was found between Refractory group and CR group (p<0.05). Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 1. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients according to low-risk NCCN-IPI. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Figure 2. Progression-free survival (A) and overall survival (B) curves of diffuse large B-cell lymphoma patients with BCR/NF-ĸB-associated mutations. Disclosures No relevant conflicts of interest to declare.
34
Soh, H., S. Park, H. J. Lee, S. J. Koh, J. P. Im, and J. S. Kim. "P104 Icariin Attenuates Intestinal Inflammation through Inhibition of the Nuclear Factor-ĸB signaling." Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i199—i200. http://dx.doi.org/10.1093/ecco-jcc/jjab232.232.
Full textAbstract:
Abstract Background Icariin is a natural flavonoid glucoside from plants in Epimedium family, known to have anti-oxidative and anti-inflammatory activities. This study investigated the effects of Icariin on nuclear factor-kappa B (NF-ĸB) signaling pathway in intestinal epithelial cells (IEC) and macrophages, and in acute and chronic murine colitis models. Methods Human IEC line COLO 205 and murine macrophage cell line RAW 264.7 were pretreated with Icariin and then stimulated with tumor necrosis factor-α (TNF-α) and lipopolysaccharide respectively for in vitro studies. The expression of pro- and anti-inflammatory cytokines were evaluated by real-time RT-PCR (TNF- α, IL-6, IL-8, IL-12, and IL-10), and the effect of Icariin on NF-ĸB signaling pathway was examined by immunoblot analysis to detect IĸBα phosphorylation and degradation. Dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10-/- mice were treated with or without Icariin for in vivo studies. The severity of colitis was evaluated by daily body weight change, colon length, and colonic tissue histopathology. Results Icariin significantly attenuated the production of pro-inflammatory cytokines and degeneration of anti-inflammatory cytokines, and alleviated IĸBα phosphorylation and degradation in both IEC and murine macrophages stimulated by TNF-α and LPS, respectively. Icariin also significantly reduced the severity of colitis in both DSS-induced acute colitis model and chronic colitis in IL-10-/- mice models. Conclusion Icariin inhibits NF-ĸB signaling in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that Icariin may be a potential novel therapeutic agent for inflammatory bowel disease.
35
Barrado-Gil, Lucía, Ana del Puerto, Inmaculada Galindo, Miguel Ángel Cuesta-Geijo, Isabel García-Dorival, Carlos Maluquer de Motes, and Covadonga Alonso. "African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation." Viruses 13, no. 6 (June 17, 2021): 1160. http://dx.doi.org/10.3390/v13061160.
Full textAbstract:
African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. Transient overexpression of UBCv1 impaired activation of NF-κB and AP-1 transcription factors induced by several agonists of these pathways. In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. Experiments aimed at mapping UBCv1 inhibitory activity indicated that this viral protein acts upstream or at the level step of IKKβ. In agreement with this, UBCv1 was able to block p65 nuclear translocation upon cytokine stimulation, a key event in NF-ĸB signaling. Additionally, A549 stably transduced for UBCv1 showed a significant decrease in the levels of NF-ĸB dependent genes. Interestingly, despite the well-defined capacity of UBCv1 to conjugate ubiquitin chains, a mutant disabled for ubiquitylation activity retained similar immunomodulatory activity as the wild-type enzyme, suggesting that the two functions are segregated. Altogether these data suggest that ASFV UBCv1 manipulates the innate immune response targeting the NF-κB and AP-1 pathways and opens new questions about the multifunctionality of this enzyme.
36
Gao, Yalong, Hejun Zhang, Xiaotian Li, Lei Li, Fanjian Li, Tuo Li, Ruilong Peng, et al. "NS1619 Alleviate Brain-Derived Extracellular Vesicle-Induced Brain Injury by Regulating BKca Channel and Nrf2/HO-1/NF-ĸB Pathway." Oxidative Medicine and Cellular Longevity 2022 (November 23, 2022): 1–20. http://dx.doi.org/10.1155/2022/2257427.
Full textAbstract:
Brain induced extracellular vesicle (BDEV) elevates after traumatic brain injury (TBI) and contributes to secondary brain injury. However, the role of BDEV in TBI remains unclear. In this study, we determined the mechanisms of BDEV in brain injury and explored whether neuroprotective drug BKca channel opener NS1619 may attenuate BDEV-induced brain injury. We injected BDEV and lactadherin, respectively, to mimic the up and downregulation of BDEV after TBI and illustrated the role of BDEV in vivo. In vitro, the membrane potential and calcium concentration of HT-22, bEnd3, and BV-2 were measured by fluorescent staining. The effects of BDEV and NS1619 on HT-22 were evaluated by CCK-8, LDH release assay, Na+/k+-ATPase activity, JC-1 staining, DHE staining, and 4-HNE staining, respectively. The role of BDEV and NS1619 on the Nrf2/HO-1/p65 pathway was also evaluated in HT-22. Finally, we administrated TBI mice with NS1619 to clarify the role of NS1619 against BDEV in vivo. Our results suggested that BDEV aggravated and lactadherin mitigated TBI-induced EB leakage, brain edema, neuronal degeneration, apoptosis, ROS level, microgliosis, MMP-9 activity, and NF-κB activation. In vitro, BDEV-caused depolarized membrane potential and calcium overload were significantly attenuated by NS1619 in HT-22, bEnd3, and BV-2. BDEV markedly decreased cell viability, Na+/k+-ATPase activity, and caused mitochondrial dysregulation, oxidative stress, and NF-ĸB activation. NS1619 pretreatment alleviated above process and enhanced antioxidant system Nrf2/HO-1 in HT-22. Finally, NS1619 administration significantly inhibited neuroinflammation response and improved TBI outcome after TBI. NS1619 treatment also reduced 4-HNE content and NF-ĸB activation and enhanced Nrf2/HO-1 pathway. Our data showed that BDEV aggravated brain injury by perturbing cell membrane potential, calcium homeostasis, oxidative stress, and neuroinflammation. The BKca channel opener NS1619 attenuated BDEV-induced pathological process in vitro and in vivo by modulating the BKca channel and Nrf2/HO-1/NF-ĸB pathway.
37
Arabzade, Amir, Yanhua Zhao, Srinidhi Varadharajan, Hsiao-Chi Chen, Kelsey Bertrand, Benjamin Deneen, and Stephen Mack. "EPEN-01. C11ORF95-RELA DICTATES ONCOGENIC TRANSCRIPTIONAL PROGRAMS TO DRIVE AGGRESSIVE SUPRATENTORIAL EPENDYMOMA." Neuro-Oncology 23, Supplement_1 (June 1, 2021): i13. http://dx.doi.org/10.1093/neuonc/noab090.051.
Full textAbstract:
Abstract Over 60% of supratentorial (ST) ependymomas harbor a gene fusion between C11orf95, an uncharacterized gene, and RELA (also known as p65), a main component of the NF-ĸB family of transcription factors. While its sufficiency to drive tumor has been established, the mechanism of tumorigenesis remains elusive. To tackle this question, we developed a natively forming mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain and performed integrative epigenomic and transcriptomic mapping. Our findings indicate that in addition to direct canonical NF-ĸB pathway activation, C11orf95-RELA (CRfus) dictates a neoplastic transcriptional program and binds to unique sites across the genome enriched with Plagl family transcription factor motifs. CRfus modulates the transcriptional landscape by recruiting transcription co-activators (Brd4, EP300, Cbp, Pol2) which are amenable to pharmacologic inhibition. Downstream CRfus target genes converge on developmental programs marked by Plagl family of transcription factors and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks, many of which contain previously unreported therapeutic leads in C11orf95-RELA ependymoma.
38
Li, Bin, Honggang Yuan, Huibing Li, Baochang Luo, Xiaoping Yu, Yanhua Wang, and Wen Liu. "Mechanism of Aquaporin-4 Up-Regulation After Traumatic Brain Injury and Preventative Action of Astragalus Polysaccharides in Mice." Journal of Biomaterials and Tissue Engineering 11, no. 6 (June 1, 2021): 1037–45. http://dx.doi.org/10.1166/jbt.2021.2502.
Full textAbstract:
Here, we aimed to clarify the anti-inflammatory function of Astragalus Polysaccharides (APS), a chemical compound derived from Astragalus membranaceus, and the action of AQP4 on brain injury. We hypothesized that APS could improve the traumatic brain injury (TBI) outcome via inhibiting expression of AQP4 in astrocytes. The present study elucidated that AQP4 was up-regulated and was effectively blocked by APS in mice with severe controlled cortical impact (CCI). Pre-treatment with APS effectively inhibited the up-regulation of AQP4 and diminished the neurological deficits in mice. Additionally, primary astrocytes treated with mechanically-injured astrocyte supernatant, to mimic TBI in vitro, showed a significant up-regulation in swelling. We confirmed various signal molecules (NF-ĸB, MAPKs, and ERK) to have a role in astrocyte swelling, after activation in trauma, and to be involved in the up-regulation of AQP4. These signal molecules also significantly decreased with APS treatment. In conclusion, our study suggests that APS attenuated neurological deficits and brain edema by decreasing AQP4 up-regulation in astrocytes following TBI in mice, via reducing NF-ĸB, MAPKs, and the ERK signal molecules.
39
Na, Heeju, Yaechan Song, and Han-Woong Lee. "Emphasis on Adipocyte Transformation: Anti-Inflammatory Agents to Prevent the Development of Cancer-Associated Adipocytes." Cancers 15, no. 2 (January 13, 2023): 502. http://dx.doi.org/10.3390/cancers15020502.
Full textAbstract:
Of the various cell types in the tumor microenvironment (TME), adipocytes undergo a dynamic transformation when activated by neighboring cancer cells. Although these adipocytes, known as cancer-associated adipocytes (CAAs), have been reported to play a crucial role in tumor progression, the factors that mediate their transformation remain elusive. In this review, we discuss the hypothesis that inflammatory signals involving NF-ĸB activation can induce lipolysis and adipocyte dedifferentiation. This provides a mechanistic understanding of CAA formation and introduces the concept of preventing adipocyte transformation via anti-inflammatory agents. Indeed, epidemiological studies indicate a higher efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in obese patients with cancer, suggesting that NSAIDs can modulate the TME. Inhibition of cyclooxygenase-2 (COX-2) and prostaglandin production leads to the suppression of inflammatory signals such as NF-ĸB. Thus, we suggest the use of NSAIDs in cancer patients with metabolic disorders to prevent the transformation of TME components. Moreover, throughout this review, we attempt to expand our knowledge of CAA transformation to improve the clinical feasibility of targeting CAAs.
40
Chen, Lanpeng, Marta De Menna, Arwin Groenewoud, George N. Thalmann, Marianna Kruithof-de Julio, and B. Ewa Snaar-Jagalska. "A NF-ĸB-Activin A signaling axis enhances prostate cancer metastasis." Oncogene 39, no. 8 (November 18, 2019): 1634–51. http://dx.doi.org/10.1038/s41388-019-1103-0.
Full text
41
Khurana, Namrata, Paarth B. Dodhiawala, Ashenafi Bulle, and Kian-Huat Lim. "Deciphering the Role of Innate Immune NF-ĸB Pathway in Pancreatic Cancer." Cancers 12, no. 9 (September 19, 2020): 2675. http://dx.doi.org/10.3390/cancers12092675.
Full textAbstract:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with no effective treatment option. A predominant hallmark of PDAC is the intense fibro-inflammatory stroma which not only physically collapses vasculature but also functionally suppresses anti-tumor immunity. Constitutive and induced activation of the NF-κB transcription factors is a major mechanism that drives inflammation in PDAC. While targeting this pathway is widely supported as a promising therapeutic strategy, clinical success is elusive due to a lack of safe and effective anti-NF-κB pathway therapeutics. Furthermore, the cell type-specific contribution of this pathway, specifically in neoplastic cells, stromal fibroblasts, and immune cells, has not been critically appraised. In this article, we highlighted seminal and recent literature on molecular mechanisms that drive NF-κB activity in each of these major cell types in PDAC, focusing specifically on the innate immune Toll-like/IL-1 receptor pathway. We reviewed recent evidence on the signaling interplay between the NF-κB and oncogenic KRAS signaling pathways in PDAC cells and their collective contribution to cancer inflammation. Lastly, we reviewed clinical trials on agents that target the NF-κB pathway and novel therapeutic strategies that have been proposed in preclinical studies.
42
Wu, Lin, Hou, Chang, Wen, Lin, and Chiang. "1,2-Bis[(3-Methoxyphenyl)Methyl]Ethane-1,2-Dicarboxylic Acid Reduces UVB-Induced Photodamage In Vitro and In Vivo." Antioxidants 8, no. 10 (October 5, 2019): 452. http://dx.doi.org/10.3390/antiox8100452.
Full textAbstract:
This study investigated the effects and mechanisms of 1,2-bis[(3-methoxyphenyl)methyl]ethane-1,2-dicarboxylic acid (S4), a sesamin derivative, on anti-inflammation and antiphotoaging in vitro and in vivo. Human skin fibroblasts were treated with S4 and did not show cytotoxicity under concentrations of 5–50 µM. In addition, S4 also reduced ultraviolet (UV)B-induced intracellular reactive oxygen species (ROS) production. Additionally, S4 inhibited UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases, activator protein-1 (AP-1), and matrix metalloproteinases (MMPs) overexpression. Furthermore, S4 also inhibited UVB-induced Smad7 protein expression and elevated total collagen content in human dermal fibroblasts. For anti-inflammatory activity, S4 inhibited UVB-induced nitric oxide synthase (i-NOS) and cyclooxygenase (COX)-2 protein expression and inhibited nuclear factor-kappaB (NF-ĸB) translocation into the nucleus. S4 ameliorated UVB-induced erythema and wrinkle formation in hairless mice. On histological observation, S4 also ameliorated UVB-induced epidermal hyperplasia and collagen degradation. S4 reduced UVB-induced MMP-1, interleukin (IL)-6, and NF-ĸB expression in the mouse skin. The results indicated that S4 had antiphotoaging and anti-inflammatory activities, protecting skin from premature aging.
43
Serreli, Gabriele, Micaela Rita Naitza, Sonia Zodio, Vera Piera Leoni, Martina Spada, Maria Paola Melis, Anna Boronat, and Monica Deiana. "Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells." Nutrients 13, no. 9 (September 10, 2021): 3152. http://dx.doi.org/10.3390/nu13093152.
Full textAbstract:
Ferulic acid (FA) is a polyphenol pertaining to the class of hydroxycinnamic acids present in numerous foods of a plant origin. Its dietary consumption leads to the formation of several phase I and II metabolites in vivo, which represent the largest amount of ferulates in the circulation and in the intestine in comparison with FA itself. In this work, we evaluated their efficacy against the proinflammatory effects induced by lipopolysaccharide (LPS) in intestinal Caco-2 cell monolayers, as well as the mechanisms underlying their protective action. LPS-induced overexpression of proinflammatory enzymes such as inducible nitric oxide synthase (iNOS) and the consequent hyperproduction of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were limited by physiological relevant concentrations (1 µM) of FA, its derivatives isoferulic acid (IFA) and dihydroferulic acid (DHFA), and their glucuronidated and sulfated metabolites, which acted upstream by limiting the activation of MAPK p38 and ERK and of Akt kinase, thus decreasing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) translocation into the nucleus. Furthermore, the compounds were found to promote the expression of Nrf2, which may have contributed to the downregulation of NF-ĸB activity. The overall data show that phase I/II metabolites retain the efficacy of their dietary free form in contrasting inflammatory response.
44
Kang, Soo-Ji, Ji-Su Jun, and Kwang-Won Hong. "Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells." International Journal of Molecular Sciences 23, no. 23 (November 22, 2022): 14519. http://dx.doi.org/10.3390/ijms232314519.
Full textAbstract:
Lacticaseibacillus rhamnosus GG (LGG) can promote intestinal health by modulating the immune responses of the gastrointestinal tract. However, knowledge about the immunomodulatory action of LGG-derived soluble factors is limited. In our previous study, we have displayed LGG-derived p75 protein on the spore surface of Bacillus subtilis. The objective of this study was to determine the effect of spore-displayed p75 (CotG-p75) on immune system by investigating transcriptional response of Caco-2 cells stimulated by CotG-p75 through RNA-sequencing (RNA-seq). RNA-seq results showed that CotG-p75 mainly stimulated genes involved in biological processes, such as response to stimulus, immune regulation, and chemotaxis. KEGG pathway analysis suggested that many genes activated by CotG-p75 were involved in NF-ĸB signaling and chemokine signaling pathways. CotG-p75 increased cytokines and chemokines such as CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, CCL20, CCL22, and IL1B essential for the immune system. In particular, CotG-p75 increased the expression levels of NF-ĸB-related genes such as NFKBIA, TNFAIP3, BIRC3, NFKB2, and RELB involved in immune and inflammatory responses. This study provides genes and pathways involved in immune responses influenced by CotG-p75. These comprehensive transcriptome profiling could be used to elucidate the immunomodulatory action of CotG-p75.
45
LEE, KUN-CHING, WEI-TING CHEN, YU-CHANG LIU, SONG-SHEI LIN, and FEI-TING HSU. "Amentoflavone Inhibits Hepatocellular Carcinoma Progression Through Blockage of ERK/NF-ĸB Activation." In Vivo 32, no. 5 (2018): 1097–103. http://dx.doi.org/10.21873/invivo.11351.
Full text
46
Puvvada, Soham D., William K. Funkhouser, Kevin Greene, Allison Deal, Haitao Chu, Albert S. Baldwin, Joel E. Tepper, and Bert H. O’Neil. "NF-ĸB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer." Oncology 78, no. 3-4 (2010): 181–88. http://dx.doi.org/10.1159/000313697.
Full text
47
Zwirchmayr, Julia, Ulrike Grienke, Scarlet Hummelbrunner, Jacqueline Seigner, Rainer de Martin, Verena M. Dirsch, and Judith M. Rollinger. "A Biochemometric Approach for the Identification of In Vitro Anti-Inflammatory Constituents in Masterwort." Biomolecules 10, no. 5 (April 28, 2020): 679. http://dx.doi.org/10.3390/biom10050679.
Full textAbstract:
Peucedanum ostruthium (L.) Koch, commonly known as masterwort, has a longstanding history as herbal remedy in the Alpine region of Austria, where the roots and rhizomes are traditionally used to treat disorders of the gastrointestinal and respiratory tract. Based on a significant NF-κB inhibitory activity of a P. ostruthium extract (PO-E), this study aimed to decipher those constituents contributing to the observed activity using a recently developed biochemometric approach named ELINA (Eliciting Nature’s Activities). This -omics tool relies on a deconvolution of the multicomponent mixture, which was employed by generating microfractions with quantitative variances of constituents over several consecutive fractions. Using an optimized and single high-performance counter-current chromatographic (HPCCC) fractionation step 31 microfractions of PO-E were obtained. 1H NMR data and bioactivity data from three in vitro cell-based assays, i.e., an NF-ĸB reporter-gene assay and two NF-κB target-gene assays (addressing the endothelial adhesion molecules E-selectin and VCAM-1) were collected for all microfractions. Applying heterocovariance analyses (HetCA) and statistical total correlation spectroscopy (STOCSY), quantitative variances of 1H NMR signals of neighboring fractions and their bioactivities were correlated. This revealed distinct chemical features crucial for the observed activities. Complemented by LC-MS-CAD data this biochemometric approach differentiated between active and inactive constituents of the complex mixture, which was confirmed by NF-κB reporter-gene testing of the isolates. In this way, four furanocoumarins (imperatorin, ostruthol, saxalin, and 2’-O-acetyloxypeucedanin), one coumarin (ostruthin), and one chromone (peucenin) were identified as NF-κB inhibiting constituents of PO-E contributing to the observed NF-ĸB inhibitory activity. Additionally, this approach also enabled the disclose of synergistic effects of the PO-E metabolites imperatorin and peucenin. In sum, prior to any isolation an early identification of even minor active constituents, e.g. peucenin and saxalin, ELINA enables the targeted isolation of bioactive constituents and, thus, to effectively accelerate the NP-based drug discovery process.
48
Zulharini S., Meirizky, Amalia Miranda, Lina Permatasari, Hilyatul Fadliyah, and Riris Istighfari Jenie. "Phaleria macrocarpa Fruit Extract Inhibits NF-ĸB Activation and Apoptosis Induction on HeLa Cells." Indonesian Journal of Cancer Chemoprevention 8, no. 1 (April 27, 2017): 9. http://dx.doi.org/10.14499/indonesianjcanchemoprev8iss1pp9-14.
Full textAbstract:
NF-κB is a transcription factor and if activated, it induces apoptosis inhibition. Phalerin from Phaleria macrocarpa fruits expected to inhibit NF-κB activation. This research is to investigate anticancer mechanism of Phaleria macrocarpa fruits extracts (EBMD) in NF-κB pathway. Molecular docking assay was performed to determine phalerin affinity to IKK. Cytotoxic activity was observed by MTT assay. Double staining was performed to determine the apoptotic cells. Docking score of phalerin to IKK is -60. The IC50 value of EBMD is 629 μg/mL. Apoptosis profile shows (shown that) many cells undergoing apoptosis after treatment. Thus, EBMD potentially inhibits activation of NF-κB pathway and triggers apoptosis on HeLa cells.Keywords : NF-κB, Phaleria macrocarpa, sel HeLa, Bcl-2, IKK, molecular docking
49
Steinecker-Frohnwieser, Bibiane, Birgit Lohberger, Nicole Eck, Anda Mann, Cornelia Kratschmann, Andreas Leithner, Werner Kullich, and Lukas Weigl. "Nuclear Magnetic Resonance Therapy Modulates the miRNA Profile in Human Primary OA Chondrocytes and Antagonizes Inflammation in Tc28/2a Cells." International Journal of Molecular Sciences 22, no. 11 (May 31, 2021): 5959. http://dx.doi.org/10.3390/ijms22115959.
Full textAbstract:
Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q™ Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1β induced changes in expression on RNA and protein level. HDAC activity an NAD(+)/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-ĸB, and a decrease in HDAC activity by NMRT was detected. NAD+/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD(+)/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1β induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-ĸB signaling.
50
Irrera, Natasha, Angela D’Ascola, Giovanni Pallio, Alessandra Bitto, Emanuela Mazzon, Federica Mannino, Violetta Squadrito, et al. "β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors." Biomolecules 9, no. 8 (July 31, 2019): 326. http://dx.doi.org/10.3390/biom9080326.
Full textAbstract:
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.