Hepatitis C virus (HCV) induced suppressor of cytokine signalling (SOCS) 3 regulates proinflammatory tumour necrosis factor (TNF)-α responses.
Item Type:Journal Article
Citation:Collins 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, 255-63
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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.
Health Research Board (HRB)
Type of material:Journal Article
Series/Report no:The Journal of Leukocyte Biology
Availability:Full text available
Subject (TCD):Immunology, Inflammation & Infection