Tristetraprolin (TTP) coordinately regulates primary and secondary cellular responses to proinflammatory stimuli
[摘要] TTPisananti‐inflammatoryproteinthatactsbybindingtoAREsinitstargetmRNAs,suchasTnfmRNA,andpromotingtheirdeadenylationanddecay.TNFreleasedfrominflammatorycellscanthenstimulategeneexpressionintissuecells,suchasfibroblasts.TodeterminewhetherTTPcouldaffectthedecayofTNF‐inducedtranscriptsinfibroblasts,weexposedprimaryembryonicfibroblastsandstablefibroblastcelllines,derivedfromWTandTTPKOmice,toTNF.Thedecayratesoftranscriptsencodedbyseveralearly‐responsegenes,includingCxcl1,Cxcl2,Ier3,Ptgs2,andLif,weresignificantlyslowedinTTP‐deficientfibroblastsafterTNFstimulation.ThesechangeswereassociatedwithTTP‐dependentincreasesinCXCL1,CXCL2,andIER3proteinlevels.TheTTP‐susceptibletranscriptscontainedmultiple,conserved,closelyspaced,potentialTTPbindingsitesintheir3′‐UTRs.WTTTP,butnotanonbindingTTPzincfingermutant,boundtoRNAprobesthatwerebasedonthemRNAsequencesofCxcl1,Cxcl2,Ptgs2,andLif.TTP‐promoteddecayoftranscriptsencodingchemokinesandotherproinflammatorymediatorsisthusacriticalpost‐transcriptionalregulatorymechanismintheresponseofsecondarycells,suchasfibroblasts,toTNFreleasedfromprimaryimmunecells...
[发布日期] [发布机构]
[效力级别] [学科分类] 生理学
[关键词] AU‐rich elements;mRNA decay;mouse embryonic fibroblasts;tumor necrosis factor [时效性]
