{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T12:30:18Z","timestamp":1774787418846,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,3,21]],"date-time":"2014-03-21T00:00:00Z","timestamp":1395360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Irish Health Research Board","award":["RP\/2007\/278"],"award-info":[{"award-number":["RP\/2007\/278"]}]},{"name":"Northern Ireland Research & Development Office"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TNF-\u03b1 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-\u03b1 and negatively regulate its NF-\u03baB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-\u03b1-mediated I\u03baB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-\u03b1-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-\u03baB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-\u03b1-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-\u03b1 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.<\/jats:p>","DOI":"10.1189\/jlb.2a1211-608rrrr","type":"journal-article","created":{"date-parts":[[2014,3,22]],"date-time":"2014-03-22T00:48:22Z","timestamp":1395449302000},"page":"255-263","source":"Crossref","is-referenced-by-count":35,"title":["Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-\u03b1 responses"],"prefix":"10.1093","volume":"96","author":[{"given":"Aideen S","family":"Collins","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suaad","family":"Ahmed","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Napoletano","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Institute of Immunology, National University of Ireland , Maynooth, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A","family":"Johnston","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Science, Queen's University of Belfast , Northern Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E","family":"Hegarty","sequence":"additional","affiliation":[{"name":"National Liver Transplant Unit, St. Vincent's University Hospital , Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cliona","family":"O'Farrelly","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Ireland"},{"name":"School of Medicine, Trinity College Dublin , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel J","family":"Stevenson","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,3,21]]},"reference":[{"key":"2023032708465434000_","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. 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