Collins, Aideen S. and Ahmed, Suaad and Napoletano, Silvia and Schroeder, Martina and Johnston, James A. and Hegarty, John E. and O'Farrelly, Cliona and Stevenson, Nigel J. (2014) Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses. Journal of Leukocyte Biology, 96 (2). pp. 255-263. ISSN 0741-5400

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Abstract

TNF-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.

Item Type:	Article
Additional Information:	The definitive published version of this article is available at 10.1189/jlb.2A1211-608RRRR
Keywords:	viral infection; inflammation; signal transduction; peripheral blood mononuclear cells; hepatocytes;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Institute of Immunology
Item ID:	6918
Identification Number:	https://doi.org/10.1189/jlb.2A1211-608RRRR
Depositing User:	Martina Schroeder
Date Deposited:	22 Jan 2016 16:18
Journal or Publication Title:	Journal of Leukocyte Biology
Publisher:	Society for Leukocyte Biology
Refereed:	Yes
Funders:	Health Research Board (HRB), Northern Ireland Research & Development Office
URI:	http://www.jleukbio.org/
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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