IL_33_ST2信号通路在疾病中作用的研究进展_曹梦远

2013-08-262013-09-1930972590309701481992－。[e-mail]··IL-33/ST2112111．7100322．323710054IL-332005IL-1。IL-33ST2NF-κBMAPKTh2。IL-33ST2Ｒ392．11A1005-5673201306-0071-05AdvancesintheroleofIL-33/ST2singlingpathwayinthediseaseCAOMeng-yuan*XUYong-niYEWeiZHANGFang-lin*DepartmentofMicrobiologyFourthMilitaryMedicalUniversityXi’an710032ChinaAbstractIL-33isamultifunctionalcytokinediscoveredin2005whichbelongstothenewmembersoftheIL-1family．ThroughitsreceptorST2IL-33activatesNF-κBandMAPKsignalingpathwaypromotesproductionofTh2cytokinesandplaysanimportantroleintheoccurrenceaswellasthedevelopmentofmanydiseases．KeywordsIL-33ST2DiseasesIL-332005IL-1IL-1βIL-18IL-1。IL-33ST2、Th2、。IL-33/ST2。1IL-331．1IL-33IL-33Baekkevold1DVS27“”。IL-3399p24．118000270IL-331919qc126650%。IL-33——IL-33IL-33IL-1β。Ｒoussel2IL-3340～58IL-33IL-33H2A-H2B。1．2IL-33IL-33、、。Baekkevold1ＲT-PCＲcDNAIL-33mＲNA。IL-33、、、、、、3。1．3IL-33IL-1βIL-18IL-33·17·201312416ProginMicrobiolImmunolDec．2013Vol．41No．6DOI:10.13309/j.cnki.pmi.2013.06.030。Schmitz330000IL-33-1caspases-1。Talabot-Ayer4IL-33caspases-3caspases-7175178。Luthi5caspase-3caspase-7IL-33。Lefrancais6IL-33、G3IL-3395-270IL-3399-270IL-33109-270caspases-1caspases-1IL-334－57。Cayrol8caspas-es-1IL-33。IL-33。1．4IL-33IL-33IL-33IL-33ST2。Carriere9IL-33。IL-33IL-33。IL-33ST2。IL-33TIL-4、IL-5IL-13Th23Th210。IL-33、NKNKTTh111－13。IL-33M21415Th116。2IL-33ST22．1ST2Tominaga171989BALB/c-3T3ST2IL-1IL-1ＲToll/IL-1Ｒ1605β-5α-。Toll/IL-1Ｒ3IL-1Ｒ、Toll。ST2sST2、ST2L、ST2VST2LV4。sST2ST2ST2LST2。mＲNA。ST2VST2LVST2ST2CST2VST2LST2LV。2．2ST2Kumar18NorthernblotST2。、、、114kb、、215kb412kb。ST2ST2V、、、、、、、、。Suzukawa19ST2Th2ST2。3IL-33/ST2IL-33ST2。IL-33L-33Ｒ1ST2IL-1IL-1ＲAcPIL-1ＲAcPST2IL-33ST23。IL-33Th2。IL-33ST2IL-1ＲAcP88MyD88、IL-1IＲAK6TＲAF6MAP-KKMAPKKc-junNJNK-1AP-1。TＲAF6-κBNF-κBNF-κBTh2IL-4、IL-5IL-13。IL-33/ST2。sST2IL-33320。IL-33sST23。IL-1ＲAcPsST2-IL-33IL-33/ST221。IL-1IL-1/TollIL-1Ｒ8SIGIＲＲTIＲ8IL-33SIGIＲＲ·27·201312416ProginMicrobiolImmunolDec．2013Vol．41No．6ST2LIL-33Ｒ2IL-33/ST22122。4IL-33/ST24．14．1．1Hazlett23BALB/cB6IL-33IL-33rIL-33。rIL-33Th1IFN-γTh2IL-4。IL-33Th2Th1。Espinassous24IL-33ST2LTNF-γ。Alves-Filho25IL-33PBSIL-33。4．1．2IL-33/ST2。Becerra26sST2sST2sST2。Jones27TheilerIL-33IL-33。Hudson28IL-33ST2Th2。4．1．3Ｒoth29IL-33sST2。Vol-arevic30Erhardt31IL-33ST2CD4+Th2NKTTh2caspase-3Bcl-2p-EＲK。4．1．4IL-33。Humphreys32IL-33。TrichurismurisIL-33mＲ-NAIL-33T．muris。Sanada33IL-33。IL-33。Miller34IL-33。IL-33caspase。4．24．2．1Th2T、。、、IL-33DAMPs。Prefontaine35IL-33mＲNA。ST2IL-33IL-33ST2IL-33IL-5、IL-13TST2IL-536-38。IL-33/ST2。4．2．2IL-33、、CD68+39。IL-33。Xu40IL-33IL-1、IL-6、IL-13rIL-33ST2。ST2IL-33/ST2IL-6、IL-12TNF-αNF-κBＲANKLmＲNA39。4．2．3SLESLE·37·201312416ProginMicrobiolImmunolDec．2013Vol．41No．641。SLE。42SLEIL-33IL-33SLEIL-33SLEIL-33SLE。SLEIL-33CSLEIL-33SIE。4．3、、。Choi43IL-33ST2/TＲAF6/Akt/eNOSNO。IL-33。WesternblotIL-33AkteNOSNO。IL-33VEGFIL-33VEGF。Wong44PI3K/AktTＲAF6TＲAF6PI3K/AktLPSPollet45TＲAF6LPS。Min46ＲANKLTＲAF6PI3K/Akt/eNOSNO。ChoiIL-33TＲAF6PI3K/Akt/eNOS43。5IL-33/ST2。IL-33/ST2。1BaekkevoldESＲoussigneMYamanakaTetal．MolecularcharacterizationofNF-HEVanuclearfactorpreferentiallyex-pressedinhumanhighendothelialvenulesJ．AmJPathol2003163169-79．2ＲousselLErardMCayrolCetal．MolecularmimicrybetweenIL-33andKSHVforattachmenttochromatinthroughtheH2A-H2BacidicpocketJ．EMBOＲep20089101006-1012．3SchmitzJOwyangAOldhamEetal．IL-33aninterleukin-1-likecytokinethatsignalsviatheIL-1receptor-relatedproteinST2andinducesThelpertype2-associatedcytokinesJ．Immunity2005235479-490．4Talabot-AyerDLamacchiaCGabayCetal．Interleukin-33isbiologicallyactiveindependentlyofcaspase-1cleavageJ．JBiolChem20092842919420-19426．5LuthiAUCullenSPMcNeelaEAetal．Suppressionofinter-leukin-33bioactivitythroughproteolysisbyapoptoticcaspasesJ．Immunity200931184-98．6LefrancaisEＲogaSGautierVetal．IL-33isprocessedintomaturebioactiveformsbyneutrophilelastaseandcathepsinGJ．ProcNatlAcadSciUSA201210951673-1678．7AliSNguyenDQFalkWetal．Caspase3inactivatesbiologi-callyactivefulllengthinterleukin-33asaclassicalcytokinebutdoesnotprohibitnucleartranslocationJ．BiochemBiophysＲesCommun201039131512-1516．8CayrolCGirardJP．TheIL-1-likecytokineIL-33isinactivatedaftermaturationbycaspase-1J．ProcNatlAcadSciUSA2009106229021-9026．9CarriereVＲousselLOrtegaNetal．IL-33theIL-1-likecyto-kineligandforST2receptorisachromatin-associatednuclearfactorinvivoJ．ProcNatlAcadSciUSA20071041282-287．10Komai-KomaMXuDLiYetal．IL-33isachemoattractantforhumanTh2cellsJ．EurJImmunol200737102779-2786．11MoulinDDonzeOTalabot-AyerDetal．InterleukinIL-33inducesthereleaseofpro-inflammatorymediatorsbymastcellsJ．Cytokine2007403216-225．12SmithgallMDComeauMＲYoonBＲetal．IL-33amplifiesbothTh1-andTh2-typeresponsesthroughitsactivityonhumanbasophilsallergen-reactiveTh2cellsiNKTandNKcellsJ．IntImmunol20082081019-1030．13BourgeoisEVanLPSamsonMetal．Thepro-Th2cytokineIL-33directlyinteractswithinvariantNKTandNKcellstoin-duceIFN-gammaproductionJ．EurJImmunol20093941046-1055．14Kurowska-StolarskaMStolarskiBKewinPetal．IL-33am-plifiesthepolarizationofalternativelyactivatedmacrophagesthatcontributetoairwayinflammationJ．JImmunol2009183106469-6477．15Ｒank