Elk‐3 is a KLF4‐regulated gene that modulates the phagocytosis of bacteria by macrophages

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

关键词: gene regulation;    inflammation;    infection;    heme oxygenase‐;    1;   

DOI  :  10.1189/jlb.4A0214-087R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ETSfamilyproteinsplayaroleinimmuneresponses.Auniquememberofthisfamily,Elk‐3,isatranscriptionalrepressorthatregulatestheexpressionofHO‐1.Elk‐3isverysensitivetotheeffectsofinflammatorymediatorsandisdown‐regulatedbybacterialendotoxin(LPS).Inthepresentstudy,exposureofmousemacrophagestoEscherichiacoliLPSresultedindecreased,full‐length,andsplice‐variantisoformsofElk‐3.WeisolatedtheElk‐3promoteranddemonstratedthatLPSalsodecreasedpromoteractivity.TheElk‐3promotercontainsGC‐richregionsthatareputativebindingsitesforzinc‐fingertranscriptionfactors,suchasSp1andKLFs.MutationoftheGC‐richregionfrombp–613to–603bluntedLPS‐induceddown‐regulationoftheElk‐3promoter.SimilartotheLPSresponse,coexpressionofKLF4ledtorepressionofElk‐3promoteractivity,whereascoexpressionofSp1increasedactivity.ChIPassaysrevealedthatKLF4bindingtotheElk‐3promoterwasincreasedbyLPSexposure,andSp1bindingwasdecreased.Thus,down‐regulationofElk‐3bybacterialLPSisregulated,inpart,bythetranscriptionalrepressorKLF4.OverexpressionofElk‐3,inthepresenceofE.colibacteria,resultedindecreasedmacrophagephagocytosis.TodeterminewhetherlimitedexpressionofHO‐1maycontributetothisresponse,weexposedHO‐1‐deficientbonemarrow‐derivedmacrophagestoE.coliandfoundacomparablereductioninbacterialphagocytosis.Thesedatasuggestthatdown‐regulationofElk‐3andthesubsequentinductionofHO‐1areimportantformacrophagefunctionduringtheinflammatoryresponsetoinfection...

【 授权许可】

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