Opioid‐induced chemokine expression requires NF‐κB activity: the role of PKCζ

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

关键词: inflammation;    DAMGO;    CCL2;   

DOI  :  10.1189/jlb.0710402

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Opioidreceptoragonistsinducebroadimmunomodulatoryactivity,whichsubstantiallyaltershostdefenseandtheinflammatoryresponse.PreviousstudieshaveshownthattheMORselectiveagonistDAMGOhasthecapacitytoincreasetheexpressionoftheproinflammatorychemokinesCCL2,CCL5,andCXCL10inhumanPBMCs.NF‐κBisatranscriptionfactorthatplaysapivotalroleininnateandadaptiveimmuneresponses.WereportthatNF‐κBisavitalplayerintheDAMGO‐induced,MOR‐mediatedregulationofchemokineexpression.ResultsshowthatNF‐κBinhibitorspreventtheinductionofCCL2expressioninresponsetoDAMGOadministrationandthattheNF‐κBsubunit,p65,isphosphorylatedatserineresidues311and536inresponsetoMORactivation.Furthermore,wedemonstratethatPKCζisphosphorylatedfollowingDAMGO‐inducedMORactivation,andthiskinaseisessentialforNF‐κBactivationaswellasCCL2expressionandtranscriptionalactivity.Finally,ChIPanalysisshowsthatDAMGOadministrationinducesbindingofp65totheenhancerregionoftheCCL2promoter.ThesedataareconsistentwiththenotionthatMORactivationpromotesaproinflammatoryresponse,whichinvolvesNF‐κBactivation.OurresultsalsosuggestasignificantandnovelroleforPKCζasanessentialparticipantintheMOR‐mediatedregulationofproinflammatorychemokineexpression...

【 授权许可】

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