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dc.contributor.authorO'FARRELLY, CLIONAen
dc.contributor.authorSTEVENSON, NIGELen
dc.date.accessioned2015-12-14T16:02:35Z
dc.date.available2015-12-14T16:02:35Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationCollins AS, Ahmed S Napoletano S, Schroeder M, Johnston JA, Hegarty JE, O'Farrelly C and Stevenson NJ., Hepatitis C virus (HCV) induced suppressor of cytokine signalling (SOCS) 3 regulates proinflammatory tumour necrosis factor (TNF)-α responses., The Journal of Leukocyte Biology, 96, 2, 2014, 255-63en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/75327
dc.descriptionPUBLISHEDen
dc.description.abstractTNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α and negatively regulate its NF-κB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-α-mediated IκB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-α-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-κB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-α-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-α signal transduction and reveal a novel immune-modulatory mechanism by which HCV suppresses inflammatory responses in primary immune cells and hepatocytes, perhaps explaining mild pathology often associated with acute HCV infection.en
dc.format.extent255-63en
dc.language.isoenen
dc.relation.ispartofseriesThe Journal of Leukocyte Biologyen
dc.relation.ispartofseries96en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectHepatitis Cen
dc.titleHepatitis C virus (HCV) induced suppressor of cytokine signalling (SOCS) 3 regulates proinflammatory tumour necrosis factor (TNF)-α responses.en
dc.typeJournal Articleen
dc.contributor.sponsorHealth Research Board (HRB)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/stevennjen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ofarreclen
dc.identifier.rssinternalid92986en
dc.identifier.doihttp://dx.doi.org/10.1189/jlb.2A1211-608RRRRen
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.orcid_id0000-0002-6966-9314en


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