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

[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...

[学科分类] 生理学

[关键词] endotoxin;TLR4;ISGF3;NF‐κB;STAT