Sulforaphane inhibits multiple inflammasomes through an Nrf2‐independent mechanism

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

关键词: caspase‐;    1;    IL‐;    1;    NLRP1;    NLRP3;    inflammation;   

DOI  :  10.1189/jlb.3A0415-155RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theinflammasomesareintracellularcomplexesthathaveanimportantroleincytosolicinnateimmunesensingandpathogendefense.Inflammasomesensorsdetectadiversityofintracellularmicrobialligandsandendogenousdangersignalsandactivatecaspase‐1,thusinitiatingmaturationandreleaseoftheproinflammatorycytokinesinterleukin‐1βandinterleukin‐18.Theseevents,althoughcrucialtotheinnateimmuneresponse,havealsobeenlinkedtothepathologyofseveralinflammatoryandautoimmunedisorders.Thenaturalisothiocyanatesulforaphane,presentinbroccolisproutsandavailableasadietarysupplement,hasgainedattentionforitsantioxidant,anti‐inflammatory,andchemopreventiveproperties.Wediscoveredthatsulforaphaneinhibitscaspase‐1autoproteolyticactivationandinterleukin‐1βmaturationandsecretiondownstreamofthenucleotide‐bindingoligomerizationdomain‐likereceptorleucine‐richrepeatproteinsNLRP1andNLRP3,NLRfamilyapoptosisinhibitoryprotein5/NLRfamilycaspase‐1recruitmentdomain‐containingprotein4(NAIP5/NLRC4),andabsentinmelanoma2(AIM2)inflammasomereceptors.Sulforaphanedoesnotinhibittheinflammasomebydirectmodificationofactivecaspase‐1anditsmechanismisnotdependentonproteindegradationbytheproteasomeordenovoproteinsynthesis.Furthermore,sulforaphane‐mediatedinhibitionoftheinflammasomesisindependentofthetranscriptionfactornuclearfactorerythroid‐derived2‐likefactor2(Nrf2)andtheantioxidantresponse‐elementpathway,towhichmanyoftheantioxidantandanti‐inflammatoryeffectsofsulforaphanehavebeenattributed.Sulforaphanewasalsofoundtoinhibitcellrecruitmenttotheperitoneumandinterleukin‐1βsecretioninaninvivoperitonitismodelofacutegoutandtoreverseNLRP1‐mediatedmurineresistancetoBacillusanthracissporeinfection.Thesefindingsdemonstratethatsulforaphaneinhibitstheinflammasomesthroughanovelmechanismandcontributestoourunderstandingofthebeneficialeffectsofsulforaphane...

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