MechanismandregulationofNLRP3inflammasomeactivationYuanHe1,HidekiHara1,andGabrielNúñez1,*1DepartmentofPathologyandComprehensiveCancerCenter,UniversityofMichiganMedicalSchool,AnnArbor,MI48109,USAAbstractMembersofthenucleotide-bindingdomainandleucine-richrepeatcontaining(NLR)familyandthepyrinandHIN-domain(PYHIN)familycanformmultiproteincomplexestermed“inflammasomes”.Thebiochemicalfunctionofinflammasomesistoactivatecaspase-1,whichleadstothematurationofinterleukin1β(IL-1β)andIL-18andinductionofpyroptosis,aformofcelldeath.Unlikeotherinflammasomes,theNLRP3inflammasomecanbeactivatedbydiversestimuli.TheimportanceoftheNLRP3inflammasomeinimmunityandhumandiseaseshasbeenwelldocumented,butthemechanismandregulationofNLRP3inflammasomeactivationremainsunclear.InthisreviewwesummarizecurrentunderstandingofthemechanismandregulationofNLRP3inflammasomeactivation,aswellasrecentadvancesinthenon-canonicalandalternativeinflammasomepathways.KeywordsNLRP3inflammasome;K+efflux;Non-canonicalinflammasome;Alternativeinflammasome;Nek7TheNLRP3inflammasome:AcriticalcomponentofinnateimmunityandpathologicalcontributortohumandiseasesInflammasomesareagroupofcytosolicproteincomplexesthatareformedtomediatehostimmuneresponsestomicrobialinfectionandcellulardamage[1].Assemblyofaninflammasometriggersproteolyticcleavageofdormantprocaspase-1intoactivecaspase-1,whichconvertsthecytokineprecursorspro-IL-1βandpro-IL-18intomatureandbiologicallyactiveIL-1βandIL-18,respectively[2,3].MatureIL-1βisapotentproinflammatorymediatorinmanyimmunereactions,includingtherecruitmentofinnateimmunecellstothesiteofinfectionandmodulationofadaptiveimmunecells,whereasmatureIL-18isimportantfortheproductionofinterferon-γandpotentiationofcytolyticactivityofnaturalkillercellsandTcells[4].Activecaspase-1alsoinducesa*Correspondence:gabriel.nunez@umich.edu(NúñezG.),DepartmentofPathology,UniversityofMichiganMedicalSchool,4215CC,1500E.MedicalCenterDrive,AnnArbor,Michigan48109,USA.Publisher'sDisclaimer:ThisisaPDFfileofanuneditedman...
