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

[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...

[学科分类] 生理学

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