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 | |
【 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...
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201904049268579ZK.pdf | 1626KB | download |