Relevant bibliographies by topics / Type I interferon pathway / Journal articles

To see the other types of publications on this topic, follow the link: Type I interferon pathway.

Journal articles on the topic 'Type I interferon pathway'

Author: Grafiati

Published: 4 June 2021

Last updated: 2 February 2022

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'Type I interferon pathway.'

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.

Aaronson, D. S., and C. M. Horvath. "The Type I Interferon Pathway." Science Signaling 2003, no. 197 (2003): cm12. http://dx.doi.org/10.1126/stke.2003.197.cm12.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Crow, Mary K., Mikhail Olferiev, and Kyriakos A. Kirou. "Type I Interferons in Autoimmune Disease." Annual Review of Pathology: Mechanisms of Disease 14, no. 1 (2019): 369–93. http://dx.doi.org/10.1146/annurev-pathol-020117-043952.

Full text

Abstract:

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.

APA, Harvard, Vancouver, ISO, and other styles

Biskup, Edyta, Brian Daniel Larsen, Leonor Rib, et al. "Photochemotherapy Induces Interferon Type III Expression via STING Pathway." Cells 9, no. 11 (2020): 2452. http://dx.doi.org/10.3390/cells9112452.

Full text

Abstract:

DNA-damaging cancer therapies induce interferon expression and stimulate the immune system, promoting therapy responses. The immune-activating STING (Stimulator of Interferon Genes) pathway is induced when DNA or double-stranded RNA (dsRNA) is detected in the cell cytoplasm, which can be caused by viral infection or by DNA damage following chemo- or radiotherapy. Here, we investigated the responses of cutaneous T-cell lymphoma (CTCL) cells to the clinically applied DNA crosslinking photochemotherapy (combination of 8–methoxypsoralen and UVA light; 8–MOP + UVA). We showed that this treatment evokes interferon expression and that the type III interferon IFNL1 is the major cytokine induced. IFNL1 upregulation is dependent on STING and on the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS). Furthermore, 8–MOP + UVA treatment induced the expression of genes in pathways involved in response to the tumor necrosis factor, innate immune system and acute inflammatory response. Notably, a subset of these genes was under control of the STING–IFNL1 pathway. In conclusion, our data connected DNA damage with immune system activation via the STING pathway and contributed to a better understanding of the effectiveness of photochemotherapy.

APA, Harvard, Vancouver, ISO, and other styles

Watson, Samir, Lisanne Knol, Jeroen Witteveldt, and Sara Macias. "Crosstalk Between Mammalian Antiviral Pathways." Non-Coding RNA 5, no. 1 (2019): 29. http://dx.doi.org/10.3390/ncrna5010029.

Full text

Abstract:

As part of their innate immune response against viral infections, mammals activate the expression of type I interferons to prevent viral replication and dissemination. An antiviral RNAi-based response can be also activated in mammals, suggesting that several mechanisms can co-occur in the same cell and that these pathways must interact to enable the best antiviral response. Here, we will review how the classical type I interferon response and the recently described antiviral RNAi pathways interact in mammalian cells. Specifically, we will uncover how the small RNA biogenesis pathway, composed by the nucleases Drosha and Dicer can act as direct antiviral factors, and how the type-I interferon response regulates the function of these. We will also describe how the factors involved in small RNA biogenesis and specific small RNAs impact the activation of the type I interferon response and antiviral activity. With this, we aim to expose the complex and intricate network of interactions between the different antiviral pathways in mammals.

APA, Harvard, Vancouver, ISO, and other styles

Volpi, Stefano, Jessica Tsui, Marcello Mariani, et al. "Type I interferon pathway activation in COPA syndrome." Clinical Immunology 187 (February 2018): 33–36. http://dx.doi.org/10.1016/j.clim.2017.10.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Iversen, Marie B., Nina Ank, Jesper Melchjorsen та Søren R. Paludan. "Expression of Type III Interferon (IFN) in the Vaginal Mucosa Is Mediated Primarily by Dendritic Cells and Displays Stronger Dependence on NF-κB than Type I IFNs". Journal of Virology 84, № 9 (2010): 4579–86. http://dx.doi.org/10.1128/jvi.02591-09.

Full text

Abstract:

ABSTRACT Interferons (IFNs) are induced as an initial response to viral infection after recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Here, we report that different PAMPs induce type I and III IFN expression at different ratios after mucosal administration in the vaginas of mice and that Toll-like receptor 9 (TLR9) stimulation evokes a particularly strong IFN-λ response, which is essential for optimal antiviral protection. Depletion of CD11c+ cells in vivo revealed that dendritic cells (DCs) in the vaginal epithelium are a key source of type I and III IFNs during herpes simplex virus infection and after specific stimulation of TLR9. A comparison of the signaling pathways activated by TLR9 and cytoplasmic PRRs, which induced lower levels of IFN-λ, revealed that high-level induction of IFN-λ correlated with strong activation of NF-κB p65. Inhibition of the NF-κB and interferon regulatory factor 3 (IRF-3) pathways with the NEMO-binding domain peptide and small interfering RNA (siRNA), respectively, revealed that transcription of the type III IFN genes was more dependent on the NF-κB pathway than that of the type I IFN genes, which relied more on the IRF system. Thus, the type I and III IFN genes are not induced through entirely identical pathways, which indicates differential expression of these two types of IFNs under certain conditions.

APA, Harvard, Vancouver, ISO, and other styles

Feng, Jun, Paul D. De Jesus, Victoria Su, et al. "RIOK3 Is an Adaptor Protein Required for IRF3-Mediated Antiviral Type I Interferon Production." Journal of Virology 88, no. 14 (2014): 7987–97. http://dx.doi.org/10.1128/jvi.00643-14.

Full text

Abstract:

ABSTRACTDetection of cytosolic nucleic acids by pattern recognition receptors leads to the induction of type I interferons (IFNs) and elicits the innate immune response. We report here the identification of RIOK3 as a novel adaptor protein that is essential for the cytosolic nucleic acid-induced type I IFN production and for the antiviral response to gammaherpesvirus through two independent kinome-wide RNA interference screens. RIOK3 knockdown blocks both cytosolic double-stranded B-form DNA and double-stranded RNA-induced IRF3 activation and IFN-β production. In contrast, the overexpression of RIOK3 activates IRF3 and induces IFN-β. RIOK3 functions downstream of TBK1 and upstream of IRF3 activation. Furthermore, RIOK3 physically interacts with both IRF3 and TBK1 and is necessary for the interaction between TBK1 and IRF3. In addition, global transcriptome analysis shows that the expression of many gene involved antiviral responses is dependent on RIOK3. Thus, knockdown of RIOK3 inhibits cellular antiviral responses against both DNA and RNA viruses (herpesvirus and influenza A virus). Our data suggest that RIOK3 plays a critical role in the antiviral type I IFN pathway by bridging TBK1 and IRF3.IMPORTANCEThe innate immune response, such as the production of type I interferons, acts as the first line of defense, limiting infectious pathogens directly and shaping the adaptive immune response. In this study, we identified RIOK3 as a novel regulator of the antiviral type I interferon pathway. Specifically, we found that RIOK3 physically interacts with TBK1 and IRF3 and bridges the functions between TBK1 and IRF3 in the activation of type I interferon pathway. The identification of a cellular kinase that plays a role the type I interferon pathway adds another level of complexity in the regulation of innate immunity and will have implications for developing novel strategies to combat viral infection.

APA, Harvard, Vancouver, ISO, and other styles

Suspitsin, E. N., R. K. Raupov, E. M. Kuchinskaya, and M. M. Kostik. "Analysis of interferon type I signature for differential diagnosis of diseases of the immune system ( review of literature)." Russian Clinical Laboratory Diagnostics 66, no. 5 (2021): 279–84. http://dx.doi.org/10.51620/0869-2084-2021-66-5-279-284.

Full text

Abstract:

Type 1 interferons (IFN1) are both key molecules of antiviral defense and potent inflammatory mediators. In 2003, increased expression of a variety of interferon 1-regulated genes was observed in a blood cells of patients with systemic lupus erythematosus (SLE). This phenomenon was called the type 1 interferon signature (IFN1-signature). Since then, expression patterns indicating the presence of an IFN1-signature were consistently detected in a range of monogenic and complex autoimmune and autoinflammatory conditions. A quantitative indicator reflecting the degree of hyperactivation of the IFN1 pathway is known as interferon score. This review discusses the possible causes of upregulated expression of interferon 1-induced genes, the laboratory approaches to the interferon score analysis, as well as the practical use of this indicator for the diagnosis of various conditions.

APA, Harvard, Vancouver, ISO, and other styles

Harris, Bethany D., Srilalitha Kuruganti, Ashlesha Deshpande, Paul A. Goepfert, W. Winn Chatham, and Mark R. Walter. "Characterization of Type-I IFN subtype autoantibodies and activity in SLE serum and urine." Lupus 29, no. 9 (2020): 1095–105. http://dx.doi.org/10.1177/0961203320935976.

Full text

Abstract:

Background/objective Type-I interferons contribute to pathogenesis in systemic lupus erythematosus, including nephritis. Interferons consist of a family of 16 proteins yet are often characterized in patients without knowledge of the specific interferon subtypes involved. Different interferons may function in the kidneys, and other organs, relative to what is often measured in patient blood. Moreover, antibodies to interferons may potentially modulate systemic or organ-specific interferon activity. The aim of this study was to characterize global interferon activity levels and identify autoantibodies to the 12 interferon α subtypes in patient serum and urine. Methods Interferon activity levels in serum and urine were measured using an interferon bioassay. Anti-interferon and anti-cytokine autoantibodies were measured by ELISA. Serum and urine samples were also characterized for their ability to neutralize the biological activity of exogenously added interferons. Results Serum interferon activity was increased in 62% of systemic lupus erythematosus patient samples, relative to healthy donor controls, whereas binding interferon α autoantibodies to at least one interferon α subtype were found in 68% of the samples evaluated. High Systemic Lupus Erythematosus Disease Activity Index scores were significantly ( p = 0.001) associated with patient samples containing interferon α autoantibodies to three or more interferon α subtypes in their serum. Interferon α autoantibodies that potently block interferon activity were rare (∼5% of samples), but collectively bound to all 12 interferon α subtypes. Urine interferon activity and interferon α autoantibody profiles did not correlate with their serum counterparts, suggesting immune responses in systemic lupus erythematosus kidneys can be distinct from those measured in serum. Analysis of autoantibodies to 15 additional cytokines in serum identified higher frequencies of granulocyte-macrophage colony-stimulating factor and interleukin 17A autoantibodies, suggesting these signaling pathways may potentially contribute, with interferons, to systemic lupus erythematosus pathogenesis. Conclusions The measurement of autoantibodies to multiple interferon subtypes in serum and urine may provide an alternative method for following interferon-mediated systemic lupus erythematosus disease activity. The results suggest autoantibodies might be used for patient monitoring and/or identifying additional cytokine signaling pathways that are functioning in different systemic lupus erythematosus patients.

APA, Harvard, Vancouver, ISO, and other styles

Pinal-Fernandez, Iago, Maria Casal-Dominguez, Assia Derfoul, et al. "Identification of distinctive interferon gene signatures in different types of myositis." Neurology 93, no. 12 (2019): e1193-e1204. http://dx.doi.org/10.1212/wnl.0000000000008128.

Full text

Abstract:

ObjectiveActivation of the type 1 interferon (IFN1) pathway is a prominent feature of dermatomyositis (DM) muscle and may play a role in the pathogenesis of this disease. However, the relevance of the IFN1 pathway in patients with other types of myositis such as the antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) is largely unknown. Moreover, the activation of the type 2 interferon (IFN2) pathway has not been comprehensively explored in myositis. In this cross-sectional study, our objective was to determine whether IFN1 and IFN2 pathways are differentially activated in different types of myositis by performing RNA sequencing on muscle biopsy samples from 119 patients with DM, IMNM, AS, or IBM and on 20 normal muscle biopsies.MethodsThe expression of IFN1- and IFN2-inducible genes was compared between the different groups.ResultsThe expression of IFN1-inducible genes was high in DM, moderate in AS, and low in IMNM and IBM. In contrast, the expression of IFN2-inducible genes was high in DM, IBM, and AS but low in IMNM. The expression of IFN-inducible genes correlated with the expression of genes associated with inflammation and muscle regeneration. Of note, ISG15 expression levels alone performed as well as composite scores relying on multiple genes to monitor activation of the IFN1 pathway in myositis muscle biopsies.ConclusionsIFN1 and IFN2 pathways are differentially activated in different forms of myositis. This observation may have therapeutic implications because immunosuppressive medications may preferentially target each of these pathways.

APA, Harvard, Vancouver, ISO, and other styles

Mattson, Lina, Antonio Lentini, Danuta R. Gawel, et al. "Potential Involvement of Type I Interferon Signaling in Immunotherapy in Seasonal Allergic Rhinitis." Journal of Immunology Research 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/5153184.

Full text

Abstract:

Specific immunotherapy (SIT) reverses the symptoms of seasonal allergic rhinitis (SAR) in most patients. Recent studies report type I interferons shifting the balance between type I T helper cell (Th1) and type II T helper cells (Th2) towards Th2 dominance by inhibiting the differentiation of naive T cells into Th1 cells. As SIT is thought to cause a shift towards Th1 dominance, we hypothesized that SIT would alter interferon type I signaling. To test this, allergen and diluent challenged CD4+ T cells from healthy controls and patients from different time points were analyzed. The initial experiments focused on signature genes of the pathway and found complex changes following immunotherapy, which were consistent with our hypothesis. As interferon signaling involves multiple genes, expression profiling studies were performed, showing altered expression of the pathway. These findings require validation in a larger group of patients in further studies.

APA, Harvard, Vancouver, ISO, and other styles

Peng, Tao, Swathi Kotla, Roger E. Bumgarner, and Kurt E. Gustin. "Human Rhinovirus Attenuates the Type I Interferon Response by Disrupting Activation of Interferon Regulatory Factor 3." Journal of Virology 80, no. 10 (2006): 5021–31. http://dx.doi.org/10.1128/jvi.80.10.5021-5031.2006.

Full text

Abstract:

ABSTRACT The type I interferon (IFN) response requires the coordinated activation of the latent transcription factors NF-κB, interferon regulatory factor 3 (IRF-3), and ATF-2, which in turn activate transcription from the IFN-β promoter. Synthesis and subsequent secretion of IFN-β activate the Jak/STAT signaling pathway, resulting in the transcriptional induction of the full spectrum of antiviral gene products. We utilized high-density microarrays to examine the transcriptional response to rhinovirus type 14 (RV14) infection in HeLa cells, with particular emphasis on the type I interferon response and production of IFN-β. We found that, although RV14 infection results in altered levels of a wide variety of host mRNAs, induction of IFN-β mRNA or activation of the Jak/STAT pathway is not seen. Prior work has shown, and our results have confirmed, that NF-κB and ATF-2 are activated following infection. Since many viruses are known to target IRF-3 to inhibit the induction of IFN-β mRNA, we analyzed the status of IRF-3 in infected cells. IRF-3 was translocated to the nucleus and phosphorylated in RV14-infected cells. Despite this apparent activation, very little homodimerization of IRF-3 was evident following infection. Similar results in A549 lung alveolar epithelial cells demonstrated the biological relevance of these findings to RV14 pathogenesis. In addition, prior infection of cells with RV14 prevented the induction of IFN-β mRNA following treatment with double-stranded RNA, indicating that RV14 encodes an activity that specifically inhibits this innate host defense pathway. Collectively, these results indicate that RV14 infection inhibits the host type I interferon response by interfering with IRF-3 activation.

APA, Harvard, Vancouver, ISO, and other styles

Freitas, Maria Cecilia S., Yoichiro Uchida, Charles Lassman, Gabriel M. Danovitch, Ronald W. Busuttil, and Jerzy W. Kupiec-Weglinski. "Type I Interferon Pathway Mediates Renal Ischemia/Reperfusion Injury." Transplantation 92, no. 2 (2011): 131–38. http://dx.doi.org/10.1097/tp.0b013e318220586e.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Baechler, Emily C., Hatice Bilgic, and Ann M. Reed. "Type I interferon pathway in adult and juvenile dermatomyositis." Arthritis Research & Therapy 13, no. 6 (2011): 249. http://dx.doi.org/10.1186/ar3531.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Ware, Carl F., and Chris Benedict. "Innate B cells: oxymoron or validated concept?" F1000Research 1 (August 2, 2012): 8. http://dx.doi.org/10.12688/f1000research.1-8.v1.

Full text

Abstract:

B lymphocytes promote the initial innate interferon response to viral pathogens without the need for antigen receptor activation. B cell dependent IFN production requires the cytokine, lymphotoxin-β. The LTβ pathway is well known to regulate lymphoid organogenesis and homeostasis by differentiating stromal cells and macrophages. However, in response to viral pathogens these same B cell-regulated populations rapidly produce type 1 interferons. Thus, B cells act as innate effector cells via LTβ homeostatic pathways, which serve as innate host barriers to viral pathogens.

APA, Harvard, Vancouver, ISO, and other styles

Kim, Tae Hoon, Dong Sun Oh, Hi Eun Jung, Jun Chang та Heung Kyu Lee. "Plasmacytoid Dendritic Cells Contribute to the Production of IFN-β via TLR7-MyD88-Dependent Pathway and CTL Priming during Respiratory Syncytial Virus Infection". Viruses 11, № 8 (2019): 730. http://dx.doi.org/10.3390/v11080730.

Full text

Abstract:

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8+ T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection.

APA, Harvard, Vancouver, ISO, and other styles

Chee, Ana Virginia, and Bernard Roizman. "Herpes Simplex Virus 1 Gene Products Occlude the Interferon Signaling Pathway at Multiple Sites." Journal of Virology 78, no. 8 (2004): 4185–96. http://dx.doi.org/10.1128/jvi.78.8.4185-4196.2004.

Full text

Abstract:

ABSTRACT Earlier studies have shown that herpes simplex virus 1 (HSV-1) blocks the interferon response pathways, at least at two sites, by circumventing the effects of activation of protein kinase R by double-stranded RNA and interferon and through the degradation of promyelocytic leukemia protein (PML) since interferon has no antiviral effects in PML−/− cells. Here we report on two effects of viral genes on other sites of the interferon signaling pathway. (i) In infected cells, Jak1 kinase associated with interferon receptors and Stat2 associated with the interferon signaling pathway rapidly disappear from infected cells. The level of interferon alpha receptor is also reduced, albeit less drastically at times after 4 h postinfection. Other members of the Stat family of proteins were either decreased in amount or posttranslationally processed in a manner different from those of mock-infected cells. The decrease in the levels of Jak1 and Stat2 may account for the decrease in the formation of complexes consisting of Stat1 or ISGF3 and DNA sequences containing the interferon-stimulated response elements after exposure to interferon. (ii) The disappearance of Jak1 and Stat2 was related at least in part to the function of the virion host shutoff protein, the product of the viral UL41 gene. Consistent with this observation, a mutant lacking the UL41 gene and treated with interferon produced lesser amounts of a late protein (UL38) than the wild-type parent. We conclude that HSV-1 blocks the interferon signaling pathways at several sites.

APA, Harvard, Vancouver, ISO, and other styles

Darrah, Eric J., Kyle P. Stoltz, Mitchell Ledwith, and Vera L. Tarakanova. "ATM supports gammaherpesvirus replication by attenuating type I interferon pathway." Virology 510 (October 2017): 137–46. http://dx.doi.org/10.1016/j.virol.2017.07.014.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Blank, Thomas, and Marco Prinz. "Type I interferon pathway in CNS homeostasis and neurological disorders." Glia 65, no. 9 (2017): 1397–406. http://dx.doi.org/10.1002/glia.23154.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Krug, Anne, Gary D. Luker, Winfried Barchet, David A. Leib, Shizuo Akira, and Marco Colonna. "Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9." Blood 103, no. 4 (2004): 1433–37. http://dx.doi.org/10.1182/blood-2003-08-2674.

Full text

Abstract:

Abstract Natural interferon-producing cells (IPCs) specialize in the production of high levels of type 1 interferons (IFNs) in response to encapsulated DNA and RNA viruses. Here we demonstrate that the secretion of type 1 IFN in response to herpes simplex virus type 1 (HSV-1) in vitro is mediated by the toll-like receptor 9 (TLR9)/MyD88 pathway. Moreover, IPCs produce interleukin-12 (IL-12) in response to HSV-1 in vitro, which is also dependent on TLR9/ MyD88 signaling. Remarkably, though TLR9/MyD88-deficiency abrogates IPC responses to HSV-1 in vitro, mice lacking either MyD88 or TLR9 are capable of controlling HSV-1 replication in vivo after local infection, demonstrating that TLR9- and MyD88-independent pathways in cells other than IPCs can effectively compensate for defective IPC responses to HSV-1.

APA, Harvard, Vancouver, ISO, and other styles

Zhao, Yunjuan, Yunliang Xie та Wangen Li. "Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway". Endocrine, Metabolic & Immune Disorders - Drug Targets 19, № 5 (2019): 656–64. http://dx.doi.org/10.2174/1871530319666190301115654.

Full text

Abstract:

Background: Type 1 diabetes is a T cell-mediated autoimmune disease. Interferon γ plays a critical role in the pathogenesis of type 1 diabetes. Signal transducer and activator of transcription transduces type I interferon cytokines in T cells, leading to Th1 cell differentiation and production of interferon γ. Recent studies suggest that liraglutide reduces the plasma concentration of C-reative protein in patients with type 1 diabetes and protects β cell function in the non-obese diabetic mouse. Objective: The study aimed to explore the effect of glucagon-like peptide-1 analogue on interferon γ production and the underlying signaling pathway in vitro. Methods: Jurkat E6-1 cells were intervened with different concentrations of glucose and liraglutide during different time periods. Protein was extracted from Jurkat E6-1 cells. The target proteins (total and activated Janus kinase 2, signal transducers and activators of transcription 4 and interferon γ) were detected by Western blot. Results: Glucose stimulates interferon γ expression and activates Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and timedependent manner. Under high glucose condition, liraglutide inhibits interferon γ expression and Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and time-dependent manner. The Janus kinase responsible for liraglutide-inhibited signal transducers and activators of transcription 4 phosphorylation is Janus kinase 2, which is also required for the interferon γ induction. Finally, we demonstrated that under high glucose condition, liraglutide inhibits interferon γ expression via Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells. Conclusion: Liraglutide inhibits Jurkat E6-1 cells to produce interferon γ via the Janus kinase/signal transducers and activators of transcription signaling pathway under high glucose condition, which implies its potential in the immunoregulatory effect of type 1 diabetes.

APA, Harvard, Vancouver, ISO, and other styles

Lang, Xueting, Tiantian Tang, Tengchuan Jin, Chen Ding, Rongbin Zhou, and Wei Jiang. "TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity." Journal of Experimental Medicine 214, no. 2 (2016): 459–73. http://dx.doi.org/10.1084/jem.20160592.

Full text

Abstract:

MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)–induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid–inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways. Importantly, Trim65−/− mice are more susceptible to EMCV infection than controls and cannot produce type I interferon in vivo. Collectively, our results identify TRIM65 as an essential component for the MDA5 signaling pathway and provide physiological evidence showing that ubiquitination is important for MDA5 oligomerization and activation.

APA, Harvard, Vancouver, ISO, and other styles

Rostami-Nejad, Mohammad, Mostafa Rezaei-Tavirani, Mohammad-Mehdi Zadeh-Esmaeel, et al. "Assessment of Cytokine-Mediated Signaling Pathway Dysregulation in Arm Skin After CO2 Laser Therapy." Journal of Lasers in Medical Sciences 10, no. 4 (2019): 257–63. http://dx.doi.org/10.15171/jlms.2019.42.

Full text

Abstract:

Introduction: Laser therapy is known as an efficient approach in dermatology surgery. CO2 laser therapy is a gold standard treatment in skin surgery. This study aimed to evaluate the interferons change after CO2 laser surgery Methods: Significant differentially-expressed genes (DEGs) of arm skin after 7 days of treatment by the CO2 laser relative to the controls are downloaded from Gene Expression Omnibus (GEO) and are included in the protein-protein interaction network via a STRING database (an application of Cytoscape software). The central DEGs were identified and enriched via gene ontology by using Clue GO software. Results: A network including 78 DEGs and 100 neighbors was constructed and STAT1, MX1, ISG15, OAS1, IFIT1, IRF8, OASL, OAS2, and RSAD2 as hubs and STAT1, PTPRC, MX1, IRF8, ISG15, IL6, RORC, SAMSN1, and IFIT1 as bottlenecks were introduced. The cytokine-mediated signaling pathway, interferon gamma signaling, hepatitis C, interferon alpha/beta signaling, and the type I interferon signaling pathway were identified as 5 clusters of biological terms which are related to the central nodes. Conclusion: It can be concluded that the cytokine-mediated signaling pathway is the major pathway that is dysregulated after laser application in the treated skin.

APA, Harvard, Vancouver, ISO, and other styles

Fullam, Anthony, Lili Gu, Yvette Höhn та Martina Schröder. "DDX3 directly facilitates IKKα activation and regulates downstream signalling pathways". Biochemical Journal 475, № 22 (2018): 3595–607. http://dx.doi.org/10.1042/bcj20180163.

Full text

Abstract:

DDX3 is a DEAD-box RNA helicase that we and others have previously implicated in antiviral immune signalling pathways leading to type I interferon (IFN) induction. We previously demonstrated that it directly interacts with the kinase IKKε (IκB kinase ε), enhances it activation, and then facilitates phosphorylation of the transcription factor IRF3 by IKKε. However, the TLR7/9 (Toll-like receptor 7/9)-mediated pathway, one of the most physiologically relevant IFN induction pathways, proceeds independently of IKKε or the related kinase TBK1 (TANK-binding kinase 1). This pathway induces type I IFN production via the kinases NIK (NF-κB-inducing kinase) and IKKα and is activated when plasmacytoid dendritic cells sense viral nucleic acids. In the present study, we demonstrate that DDX3 also directly interacts with IKKα and enhances its autophosphorylation and -activation. Modulation of DDX3 expression consequently affected NIK/IKKα-mediated IRF7 phosphorylation and induction of type I interferons. In addition, alternative NF-κB (nuclear factor-κB) activation, another pathway regulated by NIK and IKKα, was also down-regulated in DDX3 knockdown cells. This substantially broadens the effects of DDX3 in innate immune signalling to pathways beyond TBK1/IKKε and IFN induction. Dysregulation of these pathways is involved in disease states, and thus, our research might implicate DDX3 as a potential target for their therapeutic manipulation.

APA, Harvard, Vancouver, ISO, and other styles

Li, Wei, Barry P. Katz, and Stanley M. Spinola. "Haemophilus ducreyi Lipooligosaccharides Induce Expression of the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase via Type I Interferons and Tumor Necrosis Factor Alpha in Human Dendritic Cells." Infection and Immunity 79, no. 8 (2011): 3338–47. http://dx.doi.org/10.1128/iai.05021-11.

Full text

Abstract:

ABSTRACTHaemophilus ducreyicauses chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in thel-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3+regulatory T (Treg) cells. We previously found that FOXP3+Treg cells are enriched in experimental lesions and thatH. ducreyiinduced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC byH. ducreyi. Neutralizing antibodies against interferon alpha/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-α) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation.H. ducreyiculture supernatant andH. ducreyilipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-α, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-κB pathways. In addition, LOS-induced IFN-β activated the JAK-STAT pathway. Blocking the LOS/Toll-like receptor 4 (TLR4) signaling pathway greatly reducedH. ducreyi-induced IDO production. These findings indicate thatH. ducreyi-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-α-dependent mechanisms and the MAPK, NF-κB, and JAK-STAT pathways.

APA, Harvard, Vancouver, ISO, and other styles

Lange, Philip T., Eric J. Darrah, Emily P. Vonderhaar, et al. "Type I Interferon Counteracts Antiviral Effects of Statins in the Context of Gammaherpesvirus Infection." Journal of Virology 90, no. 7 (2016): 3342–54. http://dx.doi.org/10.1128/jvi.02277-15.

Full text

Abstract:

ABSTRACTThe cholesterol synthesis pathway is a ubiquitous cellular biosynthetic pathway that is attenuated therapeutically by statins. Importantly, type I interferon (IFN), a major antiviral mediator, also depresses the cholesterol synthesis pathway. Here we demonstrate that attenuation of cholesterol synthesis decreases gammaherpesvirus replication in primary macrophagesin vitroand reactivation from peritoneal exudate cellsin vivo. Specifically, the reduced availability of the intermediates required for protein prenylation was responsible for decreased gammaherpesvirus replication in statin-treated primary macrophages. We also demonstrate that statin treatment of a chronically infected host attenuates gammaherpesvirus latency in a route-of-infection-specific manner. Unexpectedly, we found that the antiviral effects of statins are counteracted by type I IFN. Our studies suggest that type I IFN signaling counteracts the antiviral nature of the subdued cholesterol synthesis pathway and offer a novel insight into the utility of statins as antiviral agents.IMPORTANCEStatins are cholesterol synthesis inhibitors that are therapeutically administered to 12.5% of the U.S. population. Statins attenuate the replication of diverse viruses in culture; however, this attenuation is not always obvious in an intact animal model. Further, it is not clear whether statins alter parameters of highly prevalent chronic herpesvirus infections. We show that statin treatment attenuated gammaherpesvirus replication in primary immune cells and during chronic infection of an intact host. Further, we demonstrate that type I interferon signaling counteracts the antiviral effects of statins. Considering the fact that type I interferon decreases the activity of the cholesterol synthesis pathway, it is intriguing to speculate that gammaherpesviruses have evolved to usurp the type I interferon pathway to compensate for the decreased cholesterol synthesis activity.

APA, Harvard, Vancouver, ISO, and other styles

Morrison, Juliet M., and Vincent R. Racaniello. "Proteinase 2Apro Is Essential for Enterovirus Replication in Type I Interferon-Treated Cells." Journal of Virology 83, no. 9 (2009): 4412–22. http://dx.doi.org/10.1128/jvi.02177-08.

Full text

Abstract:

ABSTRACT The Picornaviridae family comprises a diverse group of small RNA viruses that cause a variety of human and animal diseases. Some of these viruses are known to induce cleavage of components of the innate immune system and to inhibit steps in the interferon pathway that lead to the production of type I interferon. There has been no study of the effect of picornaviral infection on the events that occur after interferons have been produced. To determine whether members of the Enterovirus genus can antagonize the antiviral activity of interferon-stimulated genes (ISGs), we pretreated cells with alpha interferon (IFN-α) and then infected the cells with poliovirus type 1, 2, or 3; enterovirus type 70; or human rhinovirus type 16. We found that these viruses were able to replicate in IFN-α-pretreated cells but that replication of vesicular stomatitis virus, a Rhabdovirus, and encephalomyocarditis virus (EMCV), a picornavirus of the Cardiovirus genus, was completely inhibited. Although EMCV is sensitive to IFN-α, coinfection of cells with poliovirus and EMCV leads to EMCV replication in IFN-α-pretreated cells. The enteroviral 2A proteinase (2Apro) is essential for replication in cells pretreated with interferon, because amino acid changes in this protein render poliovirus sensitive to IFN-α. The addition of the poliovirus 2Apro gene to the EMCV genome allowed EMCV to replicate in IFN-α-pretreated cells. These results support an inhibitory role for 2Apro in the most downstream event in interferon signaling, the antiviral activities of ISGs.

APA, Harvard, Vancouver, ISO, and other styles

Gong, Yuanjin, Chang Chang, Xi Liu, et al. "Stimulator of Interferon Genes Signaling Pathway and its Role in Anti-tumor Immune Therapy." Current Pharmaceutical Design 26, no. 26 (2020): 3085–95. http://dx.doi.org/10.2174/1381612826666200610183048.

Full text

Abstract:

Stimulator of interferon genes is an important innate immune signaling molecule in the body and is involved in the innate immune signal transduction pathway induced by pathogen-associated molecular patterns or damage-associated molecular patterns. Stimulator of interferon genes promotes the production of type I interferon and thus plays an important role in the innate immune response to infection. In addition, according to a recent study, the stimulator of interferon genes pathway also contributes to anti-inflammatory and anti-tumor reactions. In this paper, current researches on the Stimulator of interferon genes signaling pathway and its relationship with tumor immunity are reviewed. Meanwhile, a series of critical problems to be addressed in subsequent studies are discussed as well.

APA, Harvard, Vancouver, ISO, and other styles

Xiang, Ying, Richard C. Condit, Sangeetha Vijaysri, Bertram Jacobs, Bryan R. G. Williams, and Robert H. Silverman. "Blockade of Interferon Induction and Action by the E3L Double-Stranded RNA Binding Proteins of Vaccinia Virus." Journal of Virology 76, no. 10 (2002): 5251–59. http://dx.doi.org/10.1128/jvi.76.10.5251-5259.2002.

Full text

Abstract:

ABSTRACT The vaccinia virus E3L gene encodes two double-stranded RNA binding proteins that promote viral growth and pathogenesis through suppression of innate immunity. To explore how E3L enables vaccinia virus to evade the interferon system, cells and mice deficient in the principal interferon-regulated antiviral enzymes, PKR and RNase L, were infected with wild-type vaccinia virus and strains of vaccinia virus from which E3L had been deleted (E3L-deleted strains). While wild-type virus was unaffected by RNase L and PKR, virus lacking E3L replicated only in the deficient cells. Nevertheless, E3L-deleted virus failed to replicate to high titers or to cause significant morbidity or mortality in triply deficient mice lacking RNase L, PKR, and Mx1. To investigate the underlying cause, we determined the effect of E3L on interferon regulatory factor 3 (IRF3), a transcription factor required for viral induction of subtypes of type I interferons. Results showed that IRF3 activation and interferon-β induction occurred after infections with E3L-deleted virus but not with wild-type virus. These findings demonstrate that E3L plays an essential role in the pathogenesis of vaccinia virus by blocking the interferon system at multiple levels. Furthermore, our results indicate the existence of an interferon-mediated antipoxvirus pathway that operates independently of PKR, Mx1, or the 2-5A/RNase L system.

APA, Harvard, Vancouver, ISO, and other styles

Ghodke-Puranik, Yogita, and Timothy B. Niewold. "Genetics of the type I interferon pathway in systemic lupus erythematosus." International Journal of Clinical Rheumatology 8, no. 6 (2013): 657–69. http://dx.doi.org/10.2217/ijr.13.58.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Vakaloglou, Katerina M., та Clio P. Mavragani. "Activation of the type I interferon pathway in primary Sjögrenʼs syndrome". Current Opinion in Rheumatology 23, № 5 (2011): 459–64. http://dx.doi.org/10.1097/bor.0b013e328349fd30.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Mavragani, Clio P., and Mary K. Crow. "Activation of the type I interferon pathway in primary Sjogren’s syndrome." Journal of Autoimmunity 35, no. 3 (2010): 225–31. http://dx.doi.org/10.1016/j.jaut.2010.06.012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Gallucci, Stefania, Sowmya Meka, and Ana M. Gamero. "Abnormalities of the type I interferon signaling pathway in lupus autoimmunity." Cytokine 146 (October 2021): 155633. http://dx.doi.org/10.1016/j.cyto.2021.155633.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Barman, Tarani Kanta, Rachael Racine, Jesse L. Bonin, Danielle Califano, Sharon L. Salmon, and Dennis W. Metzger. "Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza." PLOS Pathogens 17, no. 3 (2021): e1009405. http://dx.doi.org/10.1371/journal.ppat.1009405.

Full text

Abstract:

Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.

APA, Harvard, Vancouver, ISO, and other styles

Li, Jianfeng, Yin Liu, and Xuming Zhang. "Murine Coronavirus Induces Type I Interferon in Oligodendrocytes through Recognition by RIG-I and MDA5." Journal of Virology 84, no. 13 (2010): 6472–82. http://dx.doi.org/10.1128/jvi.00016-10.

Full text

Abstract:

ABSTRACT The murine coronavirus mouse hepatitis virus (MHV) induced the expression of type I interferon (alpha/beta interferon [IFN-α/β]) in mouse oligodendrocytic N20.1 cells. This induction is completely dependent on virus replication, since infection with UV light-inactivated virus could no longer induce IFN-α/β. We show that MHV infection activated both transcription factors, the IFN regulatory factor 3 (IRF-3) and nuclear factor κB (NF-κB), as evidenced by phosphorylation and nuclear translocation of IRF-3 and an increased promoter binding activity for IRF-3 and NF-κB. Furthermore, the cytoplasmic pattern recognition receptor retinoic acid-inducible gene I (RIG-I) was induced by MHV infection. Knockdown of RIG-I by small interfering RNAs blocked the activation of IRF-3 and subsequent IFN-α/β production induced by MHV infection. Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-β induction. These results demonstrate that MHV is recognized by both RIG-I and MDA5 and induces IFN-α/β through the activation of the IRF-3 signaling pathway. However, knockdown of RIG-I only partially blocked NF-κB activity induced by MHV infection and inhibition of NF-κB activity by a decoy peptide inhibitor had little effect on IFN-α/β production. These data suggest that activation of the NF-κB pathway might not play a critical role in IFN-α/β induction by MHV infection in oligodendrocytes.

APA, Harvard, Vancouver, ISO, and other styles

Song, Wuqi, Wenping Kao, Aixia Zhai, et al. "Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway." Biochemical and Biophysical Research Communications 438, no. 4 (2013): 619–23. http://dx.doi.org/10.1016/j.bbrc.2013.08.006.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Harman, Andrew N., Najla Nasr, Alexandra Feetham, et al. "HIV Blocks Interferon Induction in Human Dendritic Cells and Macrophages by Dysregulation of TBK1." Journal of Virology 89, no. 13 (2015): 6575–84. http://dx.doi.org/10.1128/jvi.00889-15.

Full text

Abstract:

ABSTRACTDendritic cells (DCs) and macrophages are present in the tissues of the anogenital tract, where HIV-1 transmission occurs in almost all cases. These cells are both target cells for HIV-1 and represent the first opportunity for the virus to interfere with innate recognition. Previously we have shown that both cell types fail to produce type I interferons (IFNs) in response to HIV-1 but that, unlike T cells, the virus does not block IFN induction by targeting IFN regulatory factor 3 (IRF3) for cellular degradation. Thus, either HIV-1 inhibits IFN induction by an alternate mechanism or, less likely, these cells fail to sense HIV-1. Here we show that HIV-1 (but not herpes simplex virus 2 [HSV-2] or Sendai virus)-exposed DCs and macrophages fail to induce the expression of all known type I and III IFN genes. These cells do sense the virus, and pattern recognition receptor (PRR)-induced signaling pathways are triggered. The precise stage in the IFN-inducing signaling pathway that HIV-1 targets to block IFN induction was identified; phosphorylation but not K63 polyubiquitination of TANK-binding kinase 1 (TBK1) was completely inhibited. Two HIV-1 accessory proteins, Vpr and Vif, were shown to bind to TBK1, and their individual deletion partly restored IFN-β expression. Thus, the inhibition of TBK1 autophosphorylation by binding of these proteins appears to be the principal mechanism by which HIV-1 blocks type I and III IFN induction in myeloid cells.IMPORTANCEDendritic cells (DCs) and macrophages are key HIV target cells. Therefore, definition of how HIV impairs innate immune responses to initially establish infection is essential to design preventative interventions, especially by restoring initial interferon production. Here we demonstrate how HIV-1 blocks interferon induction by inhibiting the function of a key kinase in the interferon signaling pathway, TBK1, via two different viral accessory proteins. Other viral proteins have been shown to target the general effects of TBK1, but this precise targeting between ubiquitination and phosphorylation of TBK1 is novel.

APA, Harvard, Vancouver, ISO, and other styles

Ge, Rui, Yi Zhou, Rui Peng, et al. "Conservation of the STING-Mediated Cytosolic DNA Sensing Pathway in Zebrafish." Journal of Virology 89, no. 15 (2015): 7696–706. http://dx.doi.org/10.1128/jvi.01049-15.

Full text

Abstract:

ABSTRACTZebrafish (Danio rerio) is a unique potential model animal for dissecting innate immune signaling. Here we demonstrate that herpes simplex virus 1 (HSV-1) could infect zebrafish at its different developmental stages and trigger the expression of type I interferons (IFNs) as well as interferon-stimulated genes (ISGs) in zebrafish larvae. Silencing of zSTING, but not zMAVS, markedly attenuates the DNA virus-induced antiviral responses. Notably, a conserved serine residue (S373) is essential for the action of zSTING. Unexpectedly, zebrafish cyclic GMP-AMP synthase (cGAS) is dispensable for the STING signaling, whereas zDHX9 and zDDX41 are potential sensors for HSV-1 infectionin vivo. Taken together, this proof-of-concept study establishes the zebrafish larva as a feasible model for investigating the cytosolic DNA sensing mechanism, shedding light on the conservation of the STING antiviral signaling pathway.IMPORTANCEThe zebrafish larva provides technical advantages for understanding host-pathogen interactions. In this study, we established the zebrafish larva as a useful model for studying HSV-1 infection. HSV-1 infection triggers strong type I interferon production, which depends on STING expression. In addition, STING-mediated antiviral signaling is conserved in zebrafish. Interestingly, zDHX9 and zDDX41 are indispensable for detecting HSV-1, while cGAS is dispensable. This proof-of-concept study indicates that the zebrafish represents an amenable model for the investigation of cytosolic DNA sensing mechanisms.

APA, Harvard, Vancouver, ISO, and other styles

Le-Thi-Phuong, Thao, Gaëtan Thirion, and Jean-Paul Coutelier. "Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus." Journal of General Virology 88, no. 11 (2007): 3063–66. http://dx.doi.org/10.1099/vir.0.83242-0.

Full text

Abstract:

Two distinct pathways of gamma interferon (IFN-γ) production have been found in mice infected with lactate dehydrogenase-elevating virus. Both pathways involve natural killer cells. The first is mostly interleukin-12-independent and is not controlled by type I interferons. The second, which is suppressed by type I interferons, leads to increased levels of IFN-γ production and requires the secretion of interleukin-12. This regulation of IFN-γ production by type I interferons may help to control indirect pathogenesis induced by this cytokine.

APA, Harvard, Vancouver, ISO, and other styles

Schabmeyer, Simone Tamara, Anna Maria Kneidl, Julia Katharina Schneider, et al. "Concentration-Dependent Type 1 Interferon-Induced Regulation of MX1 and FABP3 in Bovine Endometrial Explants." Animals 11, no. 2 (2021): 262. http://dx.doi.org/10.3390/ani11020262.

Full text

Abstract:

The inadequate maternal recognition of embryonic interferon τ (IFNτ) might explain subfertility in cattle. This study aimed at modeling the inducibility of type 1 interferon receptor subunits 1/2 (IFNAR1/2), mimicking competition between IFNτ and infection-associated interferon α (IFNα), and simulating type 1 interferon pathways in vitro. Endometrial explants (n = 728 from n = 26 healthy uteri) were collected at the abattoir, challenged with IFNτ and/or IFNα in different concentrations, and incubated for 24 h. Gene expression analysis confirmed the inducibility of IFNAR1/2 within this model, it being most prominent in IFNAR2 with 10 ng/mL IFNα (p = 0.001). The upregulation of interferon-induced GTP-binding protein (MX1, classical pathway) was higher in explants treated with 300 ng/mL compared to 10 ng/mL IFNτ (p < 0.0001), whereas the non‑classical candidate fatty acid binding protein 3 (FABP3) exhibited significant downregulation comparing 300 ng/mL to 10 ng/mL IFNτ. The comparison of explants challenged with IFNτ + IFNα indicated the competition of IFNτ and IFNα downstream of the regulatory factors. In conclusion, using this well-defined explant model, interactions between infection-associated signals and IFNτ were indicated. This model can be applied to verify these findings and to mimic and explore the embryo–maternal contact zone in more detail.

APA, Harvard, Vancouver, ISO, and other styles

Flammer, Jamie R., Jana Dobrovolna, Megan A. Kennedy, et al. "The Type I Interferon Signaling Pathway Is a Target for Glucocorticoid Inhibition." Molecular and Cellular Biology 30, no. 19 (2010): 4564–74. http://dx.doi.org/10.1128/mcb.00146-10.

Full text

Abstract:

ABSTRACT Type I interferon (IFN) is essential for host defenses against viruses; however, dysregulated IFN signaling is causally linked to autoimmunity, particularly systemic lupus erythematosus. Autoimmune disease treatments rely on glucocorticoids (GCs), which act via the GC receptor (GR) to repress proinflammatory cytokine gene transcription. Conversely, cytokine signaling through cognate Jak/STAT pathways is reportedly unaffected or even stimulated by GR. Unexpectedly, we found that GR dramatically inhibited IFN-stimulated gene (ISG) expression in macrophages. The target of inhibition, the heterotrimeric STAT1-STAT2-IRF9 (ISGF3) transcription complex, utilized the GR cofactor GRIP1/TIF2 as a coactivator. Consequently, GRIP1 knockdown, genetic ablation, or depletion by GC-activated GR attenuated ISGF3 promoter occupancy, preinitiation complex assembly, and ISG expression. Furthermore, this regulatory loop was restricted to cell types such as macrophages expressing the GRIP1 protein at extremely low levels, and pharmacological disruption of the GR-GRIP1 interaction or transient introduction of GRIP1 restored RNA polymerase recruitment to target ISGs and the subsequent IFN response. Thus, type I IFN is a cytokine uniquely controlled by GR at the levels of not only production but also signaling through antagonism with the ISGF3 effector function, revealing a novel facet of the immunosuppressive properties of GCs.

APA, Harvard, Vancouver, ISO, and other styles

Amouzegar, Afsaneh, Manoj Chelvanambi, Jessica N. Filderman, Walter J. Storkus, and Jason J. Luke. "STING Agonists as Cancer Therapeutics." Cancers 13, no. 11 (2021): 2695. http://dx.doi.org/10.3390/cancers13112695.

Full text

Abstract:

The interrogation of intrinsic and adaptive resistance to cancer immunotherapy has identified lack of antigen presentation and type I interferon signaling as biomarkers of non-T-cell-inflamed tumors and clinical progression. A myriad of pre-clinical studies have implicated the cGAS/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that drives activation of type I interferons and other inflammatory cytokines, in the host immune response against tumors. The STING pathway is also increasingly understood to have other anti-tumor functions such as modulation of the vasculature and augmentation of adaptive immunity via the support of tertiary lymphoid structure development. Many natural and synthetic STING agonists have entered clinical development with the first generation of intra-tumor delivered cyclic dinucleotides demonstrating safety but only modest systemic activity. The development of more potent and selective STING agonists as well as novel delivery systems that would allow for sustained inflammation in the tumor microenvironment could potentially augment response rates to current immunotherapy approaches and overcome acquired resistance. In this review, we will focus on the latest developments in STING-targeted therapies and provide an update on the clinical development and application of STING agonists administered alone, or in combination with immune checkpoint blockade or other approaches.

APA, Harvard, Vancouver, ISO, and other styles

Vitour, Damien, Virginie Doceul, Suzana Ruscanu, Emilie Chauveau, Isabelle Schwartz-Cornil, and Stéphan Zientara. "Induction and control of the type I interferon pathway by Bluetongue virus." Virus Research 182 (March 2014): 59–70. http://dx.doi.org/10.1016/j.virusres.2013.10.027.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Ekholm, L., S. Vosslamber, A. Tjärnlund, et al. "Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies." Scandinavian Journal of Immunology 84, no. 2 (2016): 100–109. http://dx.doi.org/10.1111/sji.12449.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Taylor, Juliet M., Zachery Moore, Myles R. Minter, and Peter J. Crack. "Type-I interferon pathway in neuroinflammation and neurodegeneration: focus on Alzheimer’s disease." Journal of Neural Transmission 125, no. 5 (2017): 797–807. http://dx.doi.org/10.1007/s00702-017-1745-4.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Flammer, Jamie R., Megan A. Kennedy, Yurii Chinenov, Lionel B. Ivashkiv, and Inez Rogatsky. "187 Glucocorticoid regulation of the type I interferon-JAK/STAT signaling pathway." Cytokine 43, no. 3 (2008): 283–84. http://dx.doi.org/10.1016/j.cyto.2008.07.249.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Roy, Ethan, Baiping Wang, Hui Zheng, and Wei Cao. "TYPE I INTERFERON-MEDIATED NEUROINFLAMMATORY PROGRAM AND SYNAPSE LOSS IN ALZHEIMER’S DISEASE." Innovation in Aging 3, Supplement_1 (2019): S92. http://dx.doi.org/10.1093/geroni/igz038.349.

Full text

Abstract:

Abstract The cytokine family type I interferon (IFN) is a major innate immune mediator extensively studied in the peripheral immune responses but largely under-investigated in AD. Previously, we established that innate immune cells readily produce IFN in response to amyloid fibrils containing nucleic acids as cofactor. Here, we investigated whether IFN pathway is associated with amyloidosis in AD brain and contributes to neuroinflammation. By systemically characterizing neuroinflammation in multiple murine AD models, we established a comprehensive core AD neuroinflammation profile that includes several key proinflammatory cytokine families, among which IFN pathway is consistently activated. When hippocampal slice culture was stimulated with different forms of amyloid fibrils, nucleic acid-containing amyloid fibrils, but not heparin-containing fibrils, potently activated IFN pathway and triggered comprehensive neuroinflammation. In addition, stereotaxic administration of IFNβ induced an immune response in the brain of wild type mice analogous to the core neuroinflammatory profile associated with Aβ pathology; whereas selective IFN receptor blockade significantly blunted the ongoing microgliosis in AD models in vivo. Furthermore, IFN promoted microglia-mediated synapse uptake from neurons, which depended on the induction of complement C3, and blockade of IFN signaling significantly abolished the pathogenic synapse loss in AD brain. Consistent with the findings in mice, we found that genes stimulated by IFN were grossly upregulated in human AD brains. Therefore, type I interferon constitutes a major pathway within the neuroinflammatory network of AD and may represent a molecular target to restrain the pathogenic inflammatory responses.

APA, Harvard, Vancouver, ISO, and other styles

Simoni, Michael K., Sydnie Swanson, Monica Mainigi, and Kellie Jurado. "22732 Impact of Type-I Interferon Manipulation During Embryo Implantation and Placentation." Journal of Clinical and Translational Science 5, s1 (2021): 94–95. http://dx.doi.org/10.1017/cts.2021.644.

Full text

Abstract:

ABSTRACT IMPACT: This research will promote understanding the role of the Type-I Interferon signaling pathway during embryo implantation, potentially leading to a new diagnostic or treatment target in early pregnancy failure. OBJECTIVES/GOALS: Studies suggest interferon signaling regulation is tightly balanced between physiologic and pathophysiologic growth in early pregnancy. We propose to determine the impact of interferon-mediated inflammation on embryo implantation and early pregnancy failure in normal conditions and chronic inflammatory diseases in a novel mixed-mouse model. METHODS/STUDY POPULATION: To probe the role of type-I interferons (IFNs) in implantation, we will utilize a mouse model and non-surgically transfer both Ifnar1-/- and Ifnar1-/+ embryos into an immune-competent pseudopregnant wild-type female recipient. This will allow analysis of a litter with distinct genotypes within the same, immune-competent, uterine environment. Type-I IFN stimulation will be systemically induced with Poly-(I:C) at various time points around implantation. A similar approach will be used in mouse models of chronic inflammatory disease states associated with early pregnancy loss (e.g. systemic lupous erythematous). With this model, we will be able to control for deficiencies in maternal immune response to specifically determine the embryonic response to inflammation during implantation and development. RESULTS/ANTICIPATED RESULTS: We anticipate the Ifnar1-/+ embryos - those able to respond to Type-I IFN - and their surrounding implantation sites will exhibit more maternal-fetal barrier dysfunction in the form of impaired trophoblast fusion, improper formation of the microvascular architecture, and increased permeability of the maternal-fetal barrier, compared to embryos unable to respond to IFN. We will also conduct similar analyses in mouse models of chronic inflammatory diseases. We hypothesize these mice to have baseline endometrial inflammation that stimulated the IFN-pathway in IFN-capable embryos, producing breakdown of the maternal-fetal barrier. In these mice, we predict Ifnar1-/- embryos will show improved molecular outcomes when compared to Ifnar1-/+ embryos, and thus improved associated pregnancy outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work can insight into the immunological mechanisms that govern embryo implantation and early placentation. This could provide more pointed means for management and intervention of early pregnancy failure and/or disease states that are commonly associated with poor reproductive outcomes.

APA, Harvard, Vancouver, ISO, and other styles

Eisemann, Jutta, Petra Mühl-Zürbes, Alexander Steinkasserer, and Mirko Kummer. "Infection of mature dendritic cells with herpes simplex virus type 1 interferes with the interferon signaling pathway." Immunobiology 212, no. 9-10 (2008): 877–86. http://dx.doi.org/10.1016/j.imbio.2007.09.005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Zhou, Zhangle, Ole J. Hamming, Nina Ank, Søren R. Paludan, Anders L. Nielsen, and Rune Hartmann. "Type III Interferon (IFN) Induces a Type I IFN-Like Response in a Restricted Subset of Cells through Signaling Pathways Involving both the Jak-STAT Pathway and the Mitogen-Activated Protein Kinases." Journal of Virology 81, no. 14 (2007): 7749–58. http://dx.doi.org/10.1128/jvi.02438-06.

Full text

Abstract:

ABSTRACT Type III interferon (IFN) is a novel member of the interferon family. Type III IFN utilizes a receptor complex different from that of type I IFN, but both types of IFN induce STAT1, STAT2, and STAT3 activation. Here we describe a detailed comparison of signal transduction initiated by type I and type III IFN. Gene expression array analysis showed that IFN types I and III induced a similar subset of genes. In particular, no genes were induced uniquely by type III IFN. Next, we used chromatin immunoprecipitation (ChIP) analysis to investigate the promoter activation by types I and III IFN. The ChIP assays demonstrated that stimulation of cells with both type I and type III IFN resulted in the recruitment of ISGF3 transcription factor components to the promoter region of responsive genes and in an increase of polymerase II loading and histone acetylation. Whereas IFN type I signaling was observed for a broad spectrum of cell lines, type III IFN signaling was more restricted. The lack of IFN type III signaling was correlated with a low expression of the IL28Ra component of the IFN type III receptor, and IL28Ra overexpression was sufficient to restore IFN type III signaling. We also tested the activation of mitogen-activated protein (MAP) kinases by type III IFN and found that type III IFN relies strongly upon both p38 and JNK MAP kinases for gene induction.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!