Academic literature on the topic 'NF-ĸB'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources 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.
Journal articles on the topic "NF-ĸB"
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
Dissertations / Theses on the topic "NF-ĸB"
1
D'Ignazio, Laura. "HIF and NF-ĸB crosstalk : the role of HIF-1β as an inducer of the inflammatory response." Thesis, University of Dundee, 2018. https://discovery.dundee.ac.uk/en/studentTheses/109f002f-8795-485a-b210-9a286cbb9da2.
Full textAbstract:
Inflammation and hypoxia, or decreased oxygen availability, are two relevant conditions involved in a large variety of physiological and pathological processes, such as immune diseases and cancer. At molecular level, these stress responses are strictly orchestrated by evolutionary conserved signaling cascades, mainly driven by the transcription factors NF-kB and Hypoxia Inducible Factors (HIFs), respectively. However, over the past years, the inflammatory response has been associated with hypoxia both in immune cells and in cancer cells. The crosstalk between NF-kB and HIF is extensive, including shared activating stimuli and regulators, as well as downstream target genes. While how NF-kB regulates HIF has been already deeply studied following TNF-α induction, the activation of HIF pathway following other inflammatory stimuli was quite unexplored. In this study, the non-canonical stimulus LIGHT (TNFSF14) was included in the list of common inducers of NF-kB and HIF. LIGHT was discovered to control HIF induction under normal oxygen levels. In particular, induction of HIF-2α, at mRNA and protein levels, occurred through activation of the non-canonical NF-kB pathway and recruitment of p52 to the HIF-2α promoter. While a role for HIF-1α in restricting the NF-kB activity already emerged, the regulatory role of HIF-1β or HIF-2α in the control of the inflammatory response was poorly understood. Here, it is shown that both HIF-1β and HIF-2α are required for the full activation of the NF-kB pathways, under different inflammatory contexts. In particular, it was demonstrated that HIF-1β modulates activators and subunits involved in both canonical and non-canonical NF-kB signalling cascades at multiple levels. Interestingly, HIF-1β depletion in TNF-α- or LIGHT-induced cells triggered the apoptotic pathway, suggesting that HIF-1β is critical for cell survival. Also, HIF-1β knock-down dramatically reduced p100 levels, through repression of TRAF6, in basal conditions and upon inflammatory stimulations. Importantly, our findings depict TRAF6, a known regulator of the NF-kB activity, as a novel direct target of HIF-1β, establishing a further level of crosstalk between HIF and NF-kB. Finally, it was demonstrated that the ability of HIF-1β to control the immune response is importantly conserved among species. In Drosophila melanogaster, HIF-1β controls the longevity of flies in unstimulated conditions, as well as it regulates their susceptibility to bacterial infections and exposure to hypoxic stress. This work uncovered novel mechanisms by which HIF-1β controls the inflammatory response, suggesting a relevance for situations often characterized by hypoxia and inflammation, such as tumours or auto-immune disorders. Although pharmacological interventions modulating HIF or NF-kB in such pathological scenarios are already available, targeting specifically the pro-inflammatory HIF-1β/HIF-2α dimers might lead to the development of novel targeted therapies against the activation of specific NF-kB dimers.
2
Silva, Bruna Santos da. "Avaliação dos efeitos da dietilcarbamazina sobre os mecanismos regulatórios do NF-ĸB na lesão hepatocelular induzida pelo alcoolismo." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/13356.
Full textAbstract:
Submitted by Luiz Felipe Barbosa (luiz.fbabreu2@ufpe.br) on 2015-04-17T14:14:52Z
No. of bitstreams: 2
Tese Bruna Santos da Silva.pdf: 5490209 bytes, checksum: 3f573d8e12cce7ecb3d65c6ed869ad1f (MD5)
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)Made available in DSpace on 2015-04-17T14:14:52Z (GMT). No. of bitstreams: 2 Tese Bruna Santos da Silva.pdf: 5490209 bytes, checksum: 3f573d8e12cce7ecb3d65c6ed869ad1f (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2013-07-30
FACEPE CPqAM/FIOCRUZ
A indução da expressão gênica mediada pelo NF-B foi descrita na patogênese da doença hepática alcoólica (DHA). Dietilcarbamazina (DEC) é um fármaco derivado da piperazina com propriedades anti-inflamatórias. O presente estudo foi desenvolvido para avaliar o efeito de DEC na via do NF-B na inflamação hepática induzida pelo alcoolismo. Quarenta camundongos machos C57BL/6 foram divididos igualmente em quatro grupos: 1) grupo controle (C), que recebeu apenas água, 2) grupo tratado com DEC, que recebeu 50 mg/kg durante um período de 12 dias (DEC50), 3) o grupo alcoólico (EtOH), submetido ao consumo crônico de álcool e 4) o grupo alcoólico tratado com DEC (EtOH50), submetido ao consumo crônico de álcool e tratado com DEC. Fragmentos de fígado foram analisados por meio de microscopia de luz, imunohistoquímica e testes de western blot para avaliar vários mecanismos envolvidos na lesão hepática induzida pelo etanol, incluindo a peroxidação lipídica, marcadores inflamatórios e a ativação de fatores de transcrição. A análise histológica do grupo alcoólico mostrou dano hepatocelular evidente que foi reduzido no grupo alcóolico tratado com DEC. Os resultados da imunohistoquímica e do western blot mostraram expressão elevada de marcadores inflamatórios como MDA, TNF-, IL-1, COX-2 e iNOS nos hepatócitos do grupo EtOH. No entanto, pouca imunopositividade para estes marcadores foi detectada após tratamento com DEC. No grupo de EtOH a ativação do fator de transcrição NF-kB foi observada através de um aumento na expressão de ambos, NF-B e pNF-B, em hepatócitos. Esta expressão foi significativamente reduzida nos fígados do grupo EtOH50. A expressão da proteína IB foi medida para determinar se a ativação do NF-B seria resultado da degradação da IB. Observou-se que a expressão desta enzima era baixa no grupo EtOH, enquanto que os animais tratados com DEC tinha uma expressão elevada de IB. Os resultados do presente estudo indicam que a DEC atenua a lesão hepática alcoólica, em parte, pela inibição da ativação do NF-B e por suprimir a indução de genes dependentes do NF-B.
3
LaGuire, Tiev C. "THE EFFECTS OF AGE ON MUSCLE LOSS AND TISSUE-SPECIFIC LEVELS OF NF-ĸB AND SIRT6 PROTEINS IN RATS." DigitalCommons@CalPoly, 2013. https://digitalcommons.calpoly.edu/theses/977.
Full textAbstract:
The objective of this study was to examine the influence of age on food intake, tissue and organ mass and NF-ĸB and SIRT6 levels in various tissues. The transcription factor, Nuclear Factor Kappa-B (NF-ĸB), is associated with both catabolic and anabolic pathways of muscle metabolism and may be involved in age-related muscle loss. SIRT6 is a member of the sirtuin family of proteins that function as protein lysine deacetylases and are associated with longevity in a number of organisms. Male Sprague-Dawley rats, aged 6 months (Adult) and 21 months (Old) were fed a commercially available diet for 10-17 days. Old rats consumed less food per body weight (BW) each day than Adult rats (1.45% g diet/g BW vs. 2.4% g diet/g BW). However, when intake data were expressed as g/diet per day there was no significant difference between groups. For skeletal muscle tissue, the average mass of gastrocnemius and soleus (g muscle/g BW) was significantly lower in Old rats. Levels of NF-ĸB (p65/RelA) and SIRT6 were measured by Western blot analysis in gastrocnemius, tibialis anterior, quadriceps, soleus, lung, heart, kidney and liver. NF-ĸB levels were higher in gastrocnemius of Old rats compared to Adult rats. No significant age-specific differences in SIRT6 protein levels were noted in the tissues examined. Interestingly, when examined independent of age, levels of SIRT6 were significantly different between certain tissues. Data from this study suggest that age affects muscle loss and NF-ĸB in a tissue-specific manner. Furthermore, these findings indicate tissue-specific but not age-specific differences in SIRT6 protein levels.
4
Stogsdill, Jeffrey Alan. "Characterization of Altered Epithelial Cell Turnover and Differentiation in Embryonic Murine Lungs That Over-Express Receptors for Advanced Glycation End-Products (RAGE)." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3217.
Full textAbstract:
Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors highly expressed in the lung that modulate pulmonary inflammation during disease. However, the contributions of RAGE signaling are unknown during pulmonary organogenesis. In order to test the hypothesis that RAGE misexpression adversely affects lung morphogenesis, conditional transgenic mice were generated that over-express RAGE in alveolar type II cells of the lung. When RAGE is over-expressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. Flow cytometry and immunohistochemistry employing cell-specific markers for various distal cell types demonstrated anomalies in key epithelial cell populations resulting from RAGE up-regulation through embryonic (E) 18.5. Electron microscopy also identified significant morphological disturbances to distal cell types including separation from the basement membrane. Possible mechanisms leading to the disappearance of pulmonary tissue by increased RAGE expression were then evaluated. A time course of lung organogenesis commencing at E12.5 demonstrated that increased RAGE expression primarily alters lung morphogenesis beginning at E16.5. TUNEL immunohistochemistry and immunoblotting for active caspase-3 confirm a shift toward apoptosis in lungs from RAGE over-expressing mice when compared to wild type controls. Assaying for NF-κB also revealed elevated nuclear translocation in lungs from transgenic mice compared to controls. An RT-PCR assessment of genes regulated by NF-κB demonstrated elevated expression of Fas ligand, suggesting increased activity of the Fas-mediated signal transduction pathway in which ligand-receptor interaction triggers cell death. These data provide evidence that RAGE expression must be tightly regulated during organogenesis. Furthermore, additional elucidation of RAGE signaling potentially involved in branching morphogenesis and cell cycle abnormalities may provide insight into the progression of RAGE-mediated lung diseases.
5
West, Chris. "Design and synthesis of inhibitors of the non-canonical NF-ĸB pathway for the treatment of prostate and pancreatic cancer." Thesis, University of Strathclyde, 2016. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=29219.
Full text
6
Lorenz, Verena Natalie [Verfasser], Michael P. [Akademischer Betreuer] Schön, Matthias [Akademischer Betreuer] Dobbelstein, and Heidi [Akademischer Betreuer] Hahn. "NF-ĸB mediated signaling mechanisms in epidermal homeostasis and carcinogenesis / Verena Natalie Lorenz. Gutachter: Matthias Dobbelstein ; Heidi Hahn. Betreuer: Michael P. Schön." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1044769262/34.
Full text
7
Mersch, Sabrina [Verfasser], Andreas [Gutachter] Krieg, and Henrike [Gutachter] Heise. "Die Rolle von RIP2 bei der Aktivierung von NF-ĸB und der Regulation der Metastasierung durch XIAP / Sabrina Mersch ; Gutachter: Andreas Krieg, Henrike Heise." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1165302608/34.
Full text
8
Schmidt-Habel, Anne-Marie [Verfasser], and Rudolf [Akademischer Betreuer] Rupec. "Erkennung von Candida albicans in Keratinozyten : Vergleich muriner und humaner Keratinozyten hinsichtlich der Bedeutung des Transkriptionsfaktors NF-ĸB und der Toll-like-Rezeptoren 2 und 4 / Anne-Marie Schmidt-Habel. Betreuer: Rudolf Rupec." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1033751987/34.
Full text
9
Lorenz, Verena Natalie. "NF-ĸB mediated signaling mechanisms in epidermal homeostasis and carcinogenesis." Doctoral thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0001-BB80-3.
Full textAbstract:
Der Transkriptionsfaktor NF-κB ist von großer Bedeutung, da er verschiedene zelluläre Prozesse wie Proliferation, Apoptose, Invasion oder Inflammation beeinflusst. Im Gegensatz zu den meisten anderen Zelltypen ist in der humanen Epidermis ein wachstumsinhibierender Effekt mit der Aktivierung von NF-ĸB assoziiert. Die epidermale Homöostase dient der Aufrechterhaltung der intakten Hautbarriere und beschreibt das Gleichgewicht zwischen proliferierenden und differenzierenden epidermalen Keratinozyten. Schädliche äußere Einflüsse wie übermäßige Sonnenlichtexposition können die epidermale Homöostase stören, was zur Entstehung epidermaler Neoplasien wie aktinischer Keratosen oder Plattenepithelkarzinomen beiträgt.
Das Ziel dieser Arbeit war die Expressions- und Funktionsanalyse der einzelnen NF-κB Proteinuntereinheiten in humanen Keratinozyten in vitro. Die siRNA-vermittelte transiente Reduktion von c-Rel beeinflusste deutlich das Zellschicksal von Keratinozyten. Obwohl vorangegangene Experimente durch eine stärkere Zellproliferation nach Inhibierung der NF-ĸB Proteine p50 und p65 das Gegenteil suggerierten, konnte für die Reduktion von c Rel ein inhibierender Effekt auf das Zellwachstum festgestellt werden. Außerdem zeigten sich eine veränderte Zellzyklusphasenverteilung sowie eine Akkumulation mitotischer Zellen mit aberranter, hauptsächlich monopolarer Spindelformation. Die zusätzlich detektierte Apoptose-Induktion könnte aus dem verlängerten mitotischen Arrest der c-Rel Knockdown Keratinozyten resultieren. Insgesamt lässt sich ein regulatorischer Effekt von c-Rel beim Eintritt in die Mitose oder der mitotischen Progression vermuten, wobei die beteiligten Zielgene noch zu identifizieren sind. Des Weiteren bewirkte der c-Rel Knockdown phänotypische Veränderung von HaCaT Keratinozyten mit tendenziell spindelzellartiger Elongation und einem insgesamt veränderten Wachstumsmuster. Die Adhäsion und besonders die Wundheilung von c-Rel reduzierten HaCaT Zellen war vermindert, möglicherweise bedingt durch ein reduziertes Stressfaservorkommen. Dieser Effekt zeigte sich allerdings nicht in c Rel herunter regulierten primären Keratinozyten, was auf Mutationen der spontan immortalisierten HaCaT Keratinozytenzelllinie zurückzuführen sein könnte.
Zusammenfassend konnte in dieser Arbeit ein neuer Aspekt der einzelnen NF-ĸB Proteine aufgezeigt werden, besonders in Bezug auf die Proteinuntereinheit c-Rel. Hieraus resultiert ein besseres Verständnis der vielfältigen und komplexen Regulation von NF-κB abhängigen Funktionen und deren Effekte auf die epidermale Homöostase.
10
Bergamo, Elisa. "MOLECULAR CHARACTERIZATION OF THE INTERACTIONS BETWEEN HTLV-1 AND HTLV-2 TAX, HBZ AND APH-2 REGULATORY PROTEINS: FUNCTIONAL IMPLICATION FOR NF-ĸB AND IFN-β." Doctoral thesis, 2016. http://hdl.handle.net/11562/939593.
Full textAbstract:
I virus T-linfotrofici umani di tipo 1 e 2 (HTLV-1 e 2) sono retrovirus geneticamente correlati che causano infezioni persistenti in vivo. HTLV-1 è l'agente eziologico della leucemia delle cellule T dell’adulto (ATLL) e della mielopatia / paraparesi spastica tropicale, mentre HTLV-2 non è associato a disturbi simili ad ATLL. L’interesse principale della ricerca è stato rivolto allo studio delle proteine espresse da HTLV, Tax e HBZ e APH-2, allo scopo di comprendere il meccanismo di deregolazione dell’espressione genica indotta dal virus. Tax svolge un ruolo fondamentale nella deregolazione dei pathways cellulari coinvolti nella risposta immunitaria, nell'infiammazione, nella sopravvivenza delle cellule e nello sviluppo del cancro, mentre HBZ gioca un ruolo cruciale nella proliferazione delle cellule T. Il confronto tra le proprietà molecolari e le funzioni delle proteine Tax e HBZ di HTLV-1 con le proteine Tax e APH-2 dell’omologo HTLV-2, può portare alla identificazione dei passaggi chiave nello sviluppo della leucemia.
Lo studio condotto durante il dottorato è stato incentrato sull’interazione delle proteine regolatrici di HTLV con i fattori dell'ospite. Sono stati indagati due aspetti: a) l'interazione di Tax-1 e Tax-2 con chinasi IKK-correlate, che interagiscono tra diverse vie di segnalazione coinvolte nella proliferazione e nella sopravvivenza delle cellule tumorali; b) l'interazione di HBZ e APH-2 con i fattori cellulari che partecipano al pathway di NF-ĸB. I dati ottenuti in questo studio hanno dimostrato una nuova interazione delle proteine Tax-1 e Tax-2 con le chinasi IKKε e TBK1, coinvolte nella via dell’interferone. I risultati hanno dimostrato che le proteine Tax sono reclutate in complessi che contengono IKKε e TBK1 alterando l’attivazione del promotore dell’IFN-β. Questi risultati evidenziano un ruolo chiave di TBK1/IKKε nella regolazione della risposta dell’interferone β in presenza dell'espressione di proteine virali. Successivamente, sono stati eseguiti studi per chiarire il ruolo di APH-2 nell’interazione con i fattori cellulari del pathway di NF-ĸB rispetto al suo omologo HBZ. I risultati dimostrano che APH-2, come HBZ, interagisce con p65 e inibisce l'attivazione di NF-ĸB. Per la prima volta è stato dimostrato che APH-2 è in grado di inibire l’attivazione di NF-ĸB mediata dalle proteine Tax e differisce da HBZ nel meccanismo di questa inibizione. APH-2 interagisce con le proteine Tax, e, quando co-espressa con Tax, cambia la sua distribuzione cellulare. I dati dimostrano che APH-2 è presente nelle strutture citoplasmatiche di Tax-2 assieme ai fattori TAB2 e TRAF3 ed interagisce con TRAF3. Questi risultati supportano l’ipotesi che APH-2, diversamente da HBZ, possa essere trattenuta nei complessi citoplasmatici, limitando il suo effetto inibitorio nell’attivazione dei promotori NF-ĸB. Nel loro insieme questi studi comparativi sulle proteine regolatrici virali possono contribuire a comprendere meglio la differente patogenicità di HTLV-1 e HTLV-2.Human T-cell leukemia virus types 1 and 2 (HTLV-1 and 2) are genetically related retroviruses that cause persistent infections in vivo. HTLV-1 is the causative agent of adult T-cell leukemia (ATLL) and myelopathy/tropical spastic paraparesis, while HTLV-2 is not associated with ATLL-like disorders. Two viral proteins expressed by the HTLV-1, Tax and HBZ, are the major focus of current research that aims to understand the oncogenic mechanism of ATLL. Tax plays a pivotal role in the deregulation of cellular pathways involved in the immune response, inflammation, cell survival and cancer, whereas HBZ plays a crucial role in T cell proliferation. Comparison of HTLV-1 Tax and HBZ molecular properties and functions to the homologous HTLV-2 Tax and APH-2 proteins should provide insight into better understand the keys steps in leukemogenesis. The Ph.D. study has been focused on HTLV regulatory proteins interaction with host factors, investigating two aspects: a) Tax-1 and Tax-2 interaction with the IKK-related kinases; b) HBZ and APH-2 interaction with host factors involved in NF-ĸB pathway. The results obtained in these studies showed a novel interaction of Tax-1 and Tax-2 proteins with IKKε and TBK1 kinases. The data demonstrated that Tax proteins may be recruited in complexes that contain IKKε and TBK1, altering IFN-β promoter activation. These results highlight a key role of TBK1/IKKε in the regulation of the interferon-β response in the presence of viral protein expression. Additional analyses were performed to investigate the role of APH-2 interaction with host factors involved on NF-ĸB pathway in comparison with its homolog HBZ. The results showed that APH-2, like HBZ, interacts with p65 and inhibits NF-ĸB. I have demonstrated for the first time that APH-2 is able to inhibit Tax proteins-mediated NF-ĸB activation and that APH-2 differs from HBZ in the mechanism of inhibition. APH-2 is able to interact with Tax proteins, and when co-expressed with Tax-2, they re-localized in the cells. Moreover, the data showed that APH-2 was present in Tax-2 cytoplasmic structures containing TAB2 and TRAF3 and that APH-2 interacted with TRAF3. The recruitment of APH-2 in cytoplasmic complexes containing Tax-2 may explain the differences in inhibition of NF-ĸB pathway compared to HBZ.
Book chapters on the topic "NF-ĸB"
1
Algül, Hana, and Roland M. Schmid. "IKK/NF-ĸB/Rel in Acute Pancreatitis and Pancreatic Cancer: Torments of Tantalus." In Frontiers of Gastrointestinal Research, 166–75. Basel: KARGER, 2009. http://dx.doi.org/10.1159/000258292.
Full text
2
Bergamo, Elisa, Erica Diani, Umberto Bertazzoni, and Maria Grazia Romanelli. "A Luciferase Functional Quantitative Assay for Measuring NF-ĸB Promoter Transactivation Mediated by HTLV-1 and HTLV-2 Tax Proteins." In Methods in Molecular Biology, 79–87. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6872-5_6.
Full textConference papers on the topic "NF-ĸB"
1
Agarwal, Nitin K., Kranthi Kunkalla, and Francisco Vega. "Abstract 3605: The inhibitor of NF-ĸB kinase, IKKβ, regulates the stability of GLI1 transcription factor." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-3605.
Full text