An essential role for IFN‐β in the induction of IFN‐stimulated gene expression by LPS in macrophages

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

关键词: endotoxin;    TLR4;    ISGF3;    NF‐;    κ;    B;    STAT;   

DOI  :  10.1189/jlb.2A0414-191R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TLRagonistssuchasLPSandpoly(I:C)induceexpressionoftypeIIFNs,suchasIFN‐αand‐β,bymacrophages.ToexaminetheroleofIFN‐βintheinductionofISGsbyLPS,wecomparedtheabilityofLPStoinduceISGF3activityandISGexpressioninbonemarrow–derivedmacrophagesfromWTandIfnb1−/−mice.WefoundthatLPStreatmentactivatedISGF3andinducedexpressionofISGssuchasOas1,Mx1,Ddx58(RIG‐I),andIfih1(MDA5)inWTmacrophages,butnotinmacrophagesderivedfromIfnb1−/−miceorIfnar1−/−mice.TheinabilityofLPStoinduceactivationofISGF3andISGexpressioninIfnb1−/−macrophagescorrelatedwiththefailureofLPStoinduceactivationofSTAT1and‐2inthesecells.Consistentwiththesefindings,LPStreatmentalsofailedtoinduceISGexpressioninbonemarrow–derivedmacrophagesfromStat2KOmice.AlthoughactivationofISGF3andinductionofISGexpressionbyLPSwasabrogatedinIfnb1−/−andIfnar1−/−macrophages,activationofNF‐κBandinductionofNF‐κB‐responsivegenes,suchasTnf(TNF‐α)andIl1b(IL‐1β),werenotaffectedbydeletionofeithertheIFN‐βorIFN‐αR1genes.ThesefindingsdemonstratethatinductionofISGF3activityandISGexpressionbyLPSiscriticallydependentonintermediateproductionofIFN‐βandautocrinesignalingthroughtypeIIFNreceptors...

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