The E3 ubiquitin ligase RNF144B is LPS‐inducible in human, but not mouse, macrophages and promotes inducible IL‐1β expression

[摘要] Differencesinhumanandmouseimmuneresponsesmaypartlyreflectspecies‐specificadaptationsandcanprovideimportantinsightsintohumanimmunity.Inthisstudy,weshowthatRNF144B,whichencodesanE3ubiquitinligase,waslipopolysaccharide‐inducibleinprimaryhumanmacrophagesandinhumanmacrophage–likeTHP‐1cells.Incontrast,Rnf144bwasnotlipopolysaccharide‐inducibleinseveralmousecellpopulations,includingprimarymacrophagesfromC57BL/6andBALB/cmiceandRAW264.7macrophages.Similarly,Rnf144bwasnotup‐regulatedbyinfectionofC57BL/6micewithEscherichiacoli.AlthoughthehumanandmouseRNF144Bgeneshaveconservedtranscriptionstartsites,capanalysisofgeneexpressiondataconfirmedthattheRNF144Bpromoterdirectstranscriptioninhumanbutnotmousemacrophages.ThehumanandmouseRNF144BgenesarecontrolledbyhighlyconservedTATA‐containingpromoters,butsubtledifferencesintranscriptionfactorbindingsitesmayaccountfordifferentialregulation.Usinggenesilencing,weshowedthatRNF144Bisnecessaryforprimingofinflammasomeresponsesinprimaryhumanmacrophages.Specifically,RNF144Bpromoteslipopolysaccharide‐inducibleIL‐1bmRNAexpressionbutdoesnotregulateexpressionofseveralotherlipopolysaccharide‐induciblecytokines(e.g.,interleukin‐10,interferon‐γ)oraffectexpressionofinflammasomecomponentsorsubstrates(e.g.,procaspase‐1,pro‐interleukin‐18).Ourfindingsthusrevealedaspecies‐specificregulatorymechanismforselectiveinflammasomepriminginhumanmacrophages...

[学科分类] 生理学

[关键词] gene expression;inflammasome;inflammation;species differences;Toll‐like receptor