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1、中国病理生理杂志ChineseJournalofPathophysiology2000,16(6):567567[文章编号]1000-4718(2000)06-0567-06炎症反应Toll信号传导通路王伯瑶,黄宁,吴琦(华西医科大学感染免疫研究室病理生理教研室,四川成都610041)TollreceptorsignalingpathwayininflammationWANGBo-yao,HUANGNing,WUQi(ResearchUnitofInfection&Immunity,DepartmentofPathophysiology,WestChin
2、aUniversityofMedicalSciences,Chengdu610041,China)AReviewTollsignalingpathwaymayplayacurcialroleininductionofinflammation-associatedgeneactivation.Originally,theToll/spaetzle/Cactus-DorsalsignalingpathwayisestablishedintheDrosophilaembryonicdevelopment.Recently,theTollsignalingpathway
3、inadultDrosophilahasbeenestablishedintheinductionofantimicrobialpeptideexpression.FivehumanToll-likereceptorgenes(hTlrl-5)andonemouseToll-likereceptorgene(mTlr-4)havebeenisolated.TollandToll-likereceptorgenesencodedmoleculesaretransmembraneproteinswithanextracellularleucinerepeatdomainan
4、dacytoplasmicdomainhomologoustoIL-1receptors.TheintracellularsignalingcascadeinvolvesTube,Pelle,andCactus-DorsalcomplexinDrosophila,andMyD88,IRAK,TRAF6,NIK,-IBkinase,andIB-NFBcomplexinmammals.DorsalandNFBaretranscriptionfactors,whileCactusandIBaretheirinhibitors.Whentheinhibitorspho
5、sphorylated,thenuclearfactorsarereleasedandmoveintonucleus,leadingtoimmunegeneactivation.IthasbeenshownfrominvitrosystemthatTlr-4mediatedLPSsignalinginhumanmonocytesforexpressionofIL-1,IL-6,IL-8,andcostimulatorB7-1whichprovidessecondsignalforTcellresponse.Tlr-2canalsomediateLPSsignalingin
6、humanmonocytes,leadingtotheproductionofproinflammatorymediators.MicrobiallipoproteinsarepotentstimulatorsofIL-12productionthroughTlr-2signalingbyhumanmacrophages,andcanstimulateTlr2-dependenttranscriptionofinduciblenitricoxidesynthaseandtheproductionofnitricoxide,apowerfulmicrobicidalpath
7、way.FindingsofapointmutationofTlr-4inLPStolerantC3H/HeJmousestrainandadeletionofTlr-4inLPSresistantC57BL/10ScCrmiceprovideaninvivoevidencestronglysupportingthecrucialroleofTlrsinLPSmediatedinflammation.ItisproposedthattargetingTlrswoulddevelopnewremediesfortr
