期刊论文详细信息
Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society
MAP kinase p38α regulates type III interferon (IFN‐λ1) gene expression in human monocyte‐derived dendritic cells in response to RNA stimulation
关键词: RIG‐;    I‐;    like receptors;    signaling;    transcription;    IRF3;    NF‐;    κ;    B;   
DOI  :  10.1189/jlb.2A0114-059RR
学科分类:生理学
来源: Federation of American Societies for Experimental Biology
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【 摘 要 】

RecognitionofviralnucleicacidsleadstotypeIandtypeIIIIFNgeneexpressionandactivationofhostantiviralresponses.Atpresent,typeIIIIFNgenesaretheleastwell‐characterizedIFNtypes.Here,wedemonstratethatthep38MAPKsignalingpathwayisinvolvedinregulatingIFN‐λ1geneexpressioninresponsetovarioustypesofRNAmoleculesinhumanmoDCs.Inhibitionofp38MAPKstronglyreducedIFNgeneexpression,andoverexpressionofp38αMAPKenhancedIFN‐λ1geneexpressioninRNA‐stimulatedmoDCs.TheregulationofIFNgeneexpressionbyp38MAPKsignalingwasindependentofproteinsynthesisandthus,adirectresultofRNAstimulation.Moreover,theRIG‐I/MDA5‐MAVS‐IRF3pathwaywasrequiredforp38αMAPKtoup‐regulateIFN‐λ1promoteractivation,whereastheMyD88‐IRF7pathwaywasnotneeded,andtheregulationwasnotinvolveddirectlyinIRF7‐dependentIFN‐α1geneexpression.Thestimulatoryeffectofp38αMAPKonIFN‐λ1mRNAexpressioninhumanmoDCsdidnottakeplacedirectlyviatheactivatingTBK1/IKKɛcomplex,butrather,itoccurredthroughsomeotherparallelpathways.Furthermore,mutationsinISREandNF‐κBbindingsitesinthepromoterregionoftheIFN‐λ1geneledtoasignificantreductioninp38αMAPK‐mediatedIFNresponsesafterRNAstimulation.Altogether,ourdatasuggestthatthep38αMAPKpathwayislinkedwithRLRsignalingpathwaysandregulatestheexpressionofearlyIFNgenesafterRNAstimulationcooperativelywithIRF3andNF‐κBtoinduceantiviralresponsesfurther...

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