Hepatitis C virus (HCV)‐induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF‐α responses

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: viral infection;    inflammation;    signal transduction;    peripheral blood mononuclear cells;    hepatocytes;   

DOI  :  10.1189/jlb.2A1211-608RRRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TNF‐αisaproinflammatorycytokine,dramaticallyelevatedduringpathogenicinfectionandoftenresponsibleforinflammation‐induceddiseasepathology.SOCSproteinsareinhibitorsofcytokinesignalingandregulatorsofinflammation.Inthisstudy,wefoundthatbothSOCS1andSOCS3weretransientlyinducedbyTNF‐αandnegativelyregulateitsNF‐κB‐mediatedsignaltransduction.WediscoveredthatPBMCsfromHCV‐infectedpatientshaveelevatedendogenousSOCS3expressionbutlessTNF‐α‐mediatedIκBdegradationandproinflammatorycytokineproductionthanhealthycontrols.HCVproteinexpressioninHuh7hepatocytesalsoinducedSOCS3anddirectlyinhibitedTNF‐α‐mediatedIL‐8production.Furthermore,wefoundthatSOCS3associateswithTRAF2andinhibitsTRAF2‐mediatedNF‐κBpromoteractivity,suggestingamechanismbywhichSOCS3inhibitsTNF‐α‐mediatedsignaling.TheseresultsdemonstratearoleforSOCS3inregulatingproinflammatoryTNF‐αsignaltransductionandrevealanovelimmune‐modulatorymechanismbywhichHCVsuppressesinflammatoryresponsesinprimaryimmunecellsandhepatocytes,perhapsexplainingmildpathologyoftenassociatedwithacuteHCVinfection...

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