炎症Caspase-与相关疾病

ChineseBulletinofLifeSciences185200610Vol.18,No.5Oct.,2006Caspase12000622201203CaspaseCaspase-1-4-5-11-12CaspaseIL-1IL-1CaspaseCaspaseIL-1βIL-18Caspase-1Q556.9;R741AInflammatoryCaspaseanddiseasesMAXue-Qin1,ZHANGYa-Hui2,ZHOUZhong-Liang1,LIJia2*(1SchoolofLifeSciences,EastChinaNormalUniversity,Shanghai200062,China;2NationalCenterforDrugScreening,ShanghaiInstituteofMedicalMaterial,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai201203,China)Abstract:Caspaseisafamilyrelatedtoapoptosisandinflammatoryresponse.Inthisfamily,Caspase-1,-4,-5,-11,-12arenominatedinflammatorycaspaseswhicharemainlyrelatedtoinflammatoryresponse.InflammatoryCaspasesareresponsiblefortheprocessingofpro-inflammatorycytokineIL-1.IL-1,asaupstreamofimmuneresponse,canstimulatemanyinflammatorycytokinesandeffects,andtheninduceinflammatorydiseases,suchasneuronapoptosisandcytotoxicity,jointdestructionandpain,apoptosisoflivercell,acutepancreatitis,etc.Therefore,itisveryimportantforthetreatmentofinflammatorydiseasestoinhibittheinflammatoryCaspasesactivities.Keywords:inflammatoryCaspase;IL-1β;IL-18;inflammatorydiseases;Caspase-1inhibitors2006-01-062006-02-22(GrantKSCX1-SW-11-2)(1980)(1976)(1957)(1971)*1004-0374(2006)05-0452-05Caspase14Caspase(apoptoticinitiators)(apoptoticexecutioners)(inflammatorymediators)Caspase-2-8-9-10Caspase-3-6-7Caspase-1-4-5Caspase-11-12CaspaseCaspase4535Caspase-1β(interlukin-1βIL-1β)-18(interlukin-18IL-18)CaspaseCaspaseCaspase-1IL-1βIL-18[1]IL-1βIL-18IL-1IL-1βIL-18CaspaseCaspaseIL-1IL-1A2(COX)(NO)β-(βAPP)[2]IL-1IL-18IFN-γCaspaseCaspase1CaspaseCaspase-1Caspase31kDaIL-1βTyr-Val-His-Asp116/Ala11717kDaIL-1βIL-18Asp36Caspase-1IL-1βIL-18[3](LPS)Caspase-1IL-6TNFαIFN-γIL-1NF-κBNF-κB[4]Caspase-1Caspase-1COSDNACaspase-1CrmA(Caspase-1)COSCaspase-1ADP-(polyADP-ribosepolymerase,PARP)DNA[5]Caspase-1[6]Caspase-4Caspase-5Caspase(75%)Caspase-150%IL-1βCaspase-1caspase-4Caspase-5[7]Caspase-5Caspase-1Caspase-1Caspase-5IL-1β[8]Caspase-4Caspase-5COSCaspase-4Caspase-5FasHelaCaspase-4Caspase-4Caspase-4FasCaspase-4Fas[9]Caspase-11Caspase-1CaspaseCaspase-1Caspase-11IL-1βIL-18Caspase-1Caspase-11Caspase-1[10]Kang[11]Caspase-11Caspase-1Caspase-3Caspase-11Caspase-5Caspase-11Caspase54%LPSCaspase-5Caspase-11[7]Caspase-12Caspase-12Caspase-12Aβ(Alzheimer’sDisease)Caspase-1245418Caspase-12Caspase-12LPSIL-1βINFβIL-1NF-κBCaspase-12[12]2Caspase2.1IL-1[2]CaspaseCaspase-1IL-1IL-1βIL-18Caspase-12.1.1(amyotrophiclateralsclerosisALS),(SOD1)(SOD1G93A)ALSIL-1β2.4Caspase-1Caspasez-VAD-fmk37%Caspase-1ALSCaspase-181.5%[13]IL-1βCaspase-1BidCaspase-1BidCCaspase-3-9[14]SOD(G93R)Caspase-1ALS[15]Caspase-1ALS2.1.2(Huntington’sdisease,HD)HD7Caspase-1[16]Caspase-1Caspase-1HuntingtonOna[17]R6/2()Caspase-1NSEM17Z(Caspase-1cysteinglycine)HuntingtonCaspase-1R6/2-NSEM17ZR6/24Caspasez-VAD-fmkQna[17]R6/2HuntingtonIL-1β268%213%R6/2-NSEM17ZIL-1β,Caspase-1Caspase-1HDIL-1β2.1.3(Hypoxic/ischemic,H/I)IL-1IL-1IL-1IL-1RaCaspase-1[18]Hayashi[19]7CA1Caspase-1Caspase-3Caspase-1IL-1βCaspase-1Caspase-3CA1Caspase-1IL-1β2.2(rheumatoidarthritis,RA)(osteoarthritis,OA)RAOAIL-1βIL-18IL-1βIL-18Caspase-1IL-1β(MMPs)[20]IL-1βIL-1βCOX-2PGE2Samad[21]Caspase-14555CaspaseYVADIL-1βCOX-2PGE2PralnacasanCaspase-1-4[22],aCasase-12.3()IL-1TNFαIFN-γβ[23]Fas50µMCaspase-1YVAD-cmk50%300µMYVAD-cmk[24]CaspaseXyz033Caspase-1CaspaseIL-1βTUNNEL[25]Caspase-12.4(acutepancreatitisAP)10%~20%(severeacutepancreatitisSAP)10%,IL-1βTNF-αAP()[26]Norman[27]APIL-1βmRNA120Caspase-1Caspase-1Caspase-1Caspase-1IL-1βTNF-αRau[28]IL-18AP68APIL-18IL-18Caspase-12.5(multiplesclerosisMS)[28](Crohn’sdiseaseCD)[30](familialcoldautoinflammatorysyndromeFCAS)(neonatal-onsetmultisys-teminflammatorydisease,NOMID)[31]CaspaseCaspase3IL-1βIL-18CaspaseCaspase-1CaspaseCaspaseCaspaseCaspase-1Caspase-1-/-Fas[32~33]VertexVX-740(Pralnacasan)VX-765[34~35]Caspase[1]SahaN,MoldovanF,TardifG,etal.Interleukin-1βconvert-ingenzyme/caspase-1inhumanosteoarthritistissues.ArthritisRheum,1999,42(8):1577~1587[2]RothwellN,AllanS,ToulmondS.Theroleofinterleukin145618inacuteneurodegenerationandstroke:pathophysiologicalandtherapeuticimplications.JClinInvest,1997,100(11):2648~2652[3]LiP,AllenH,BanerjeeS,etal.MicedeficientinIL-1β-convertingenzymearedefectiveinproductionofmatureIL-1βandresistanttoendotoxicshock.Cell,1995,80(3):401~411[4]MoynaghPN.Theinterleukin-1signallingpathwayinastrocytes:akeycontributortoinflammationinthebrain.JAnat,2005,207(3):265~269[5]ChenWY,RaybuckSA,FulghumRA,etal.Expressionandpurificationofhumaninterleukin-1bconvertingenzymefromTrichoplusianiinsectcellsusingabaculovirusexpressionsystem.ProteinExprPurif,1997,9(1):69~75[6]LaunayS,HermineO,FontenayM,etal.VitalfunctionsforlethalCaspases.Oncogene,2005,24(33):5137~5148[7]LinXY,ChoiMSK,PorterAG.ExpressionanalysisofthehumanCaspase-1subfamilyrevealsspecificregulationoftheCASP5genebylipopolysaccharideandinterferon-γ.JBiolChem,2000,275(51):39920~39926[8]FabioM,KimberlyB,JurgT.Theinflammasome:amo-lecularplatformtriggeringactivationofinflammatorycaspasesandprocessingofproIL-1β,MolCell,2002,10(2):417~426