搜索
[J].,2008,27(2):67269.[14]LauKH,BaylinkDJ.Molecularmechanismofactionoffluorideonbonecells[J].BoneMinerRes,1998,13(11):166021667.[15]FujitaT,PalmieriGM.Calciumparadoxdisease:Calciumdeficien2cypromptingsecondaryhyperparathyroidismandcellularcalciumoverload[J].BoneMinerMetab,2000,18(3):1092125.[16]GofaA,DavidsonRM.NaFpotentiatesaK(+)2selectionchannelinG292osteoblasticcells[J].JMembrBiol,1996,149(3):2112219.[17],,.[J].,2005,34(10):6322634.[18],,.OPGLmRNAM2CSFmRNA[J].,2003,22(2):1152118.[19],,,.[J].,2004,23(2):1862187.[20],,.[J].,1998,17(2):75278.[21],,,.RANKLmRNA[J].,2007,26(2):1302132.[22].OPGRANKL[D].:,2006.[23],.Cbfa1/Runx2[J].,2005,17(1):40244.[24].Runx2[J].,2006,4(1):42245.[25]YamaguchiA,KomoriT,SudaT.Regulationofosteoblastdifferen2tiationmediatedbybonemorphogeneticproteins,hedgehogs,andCbfa1[J].EndocrRev,2000,21(4):3932411.:2009203214:2009208207TLR4(),()(,200011):Q51:A:100622084(2009)1922902203:Toll(TLR),,,TLRTLR,TLR4/,TLR4/CD14TLR4TLR4:Toll;Toll4;;CD14;TLR4SignalPathwayandInflammationReactionCHENJie,JIANGHong.(DepartmentofAnaesthe2siology,theNinthPeoplesHospital,SchoolofMedicine,ShanghaiJiaoTongUniversity,Shanghai200011,China)Abstract:Tolllikereceptors(TLR)areinnateimmunereceptorsrelatedtotheproteinsinDrosophilaregulatingdorsalventralpatterningduringembryogenesis.Todate,theTLRfamilyhasalsobeenfoundinmammaliancells.Tolllikereceptorsdistributewidely,whcihpresentonthecellsurfaceofinnateimmunecellsandhaverecognizemicrobialmotifs,namedaspathogen2associatedmolecularpatterns(PAMPs).TLR4isthemajorreceptorrecognizingvariousbacterialcellwallcomponentsincludinglipopolysaccharide(LPS)responseandsignalingofhumanmonocytesuponLPSfromgram2negativebacteriadependsonthepresenceandfunctionofbothCD14andTLR4,sotheTLR4/CD14signalpathwayisthemostimportantwayininflam2mationreactioninducingbyLPSVariationininnateimmunitygenessuchasTLR4,orCD14maymodulatere2sponsivenesstoLPSandotherPAMPsandthusplayaroleinthedevelopmentofatopyandrespiratorydis2ease.TLR4isassociatedwithalimentaryobesity,atherosclerosis,cardiacinfarction,asthma.Thisarticlere2viewedthedevelopmentbetweenTLR4andinflammationreaction.Keywords:Tolllikereceptor;Tolllikereceptor4;Lipopolysaccharide;CD14;InflammationreactionToll(Tolllikereceptor,TLR),[1],,,TLRTLR,,,,,,,,TLR12,TLRTLR4/(lipopo2lysaccharide,LPS)[2]CD14LPSLPSCD14,,,,LPS,:CD14,LPS2LPS,TLR4/CD14TLR4FA[3],,[4]TLR4TLR41TLR4TLR4TLR,20922009101519MedicalRecapitulate,Oct2009,Vol.15,No.19,,,[5],,TLR4[6]TLR43:(LRR),CD14,,1(interleukin21,IL21),TIR(Toll/IL21receptor),TLR4,TIR,B(nuclearfactor2B,NF2B),[7]LPSTLR4/NF2B:88(myeloiddifferentiationfactor88,MyD88);MyD88,LPSTLR4,TLR4TLR4TIRMyD88,MyD88IL21(IL21receptor2associatedkinase,IRAK),IRAKIRAK6(TNF2receptorassociationfactor6,TRAF26),TRAF26NF2B(inhibitorofNF2Bkinases,IKKs)NF2B(inhibitorofNF2B)IKKs,IKKsNF2B,,IL21IL26IL28IL212,MyD88,LPSMyD8810,TLR4,MyD88,3NF2BTLR4NF2B,,TRAF6IKKs,(TGF2activatedkinase1,TAK1),MKK6(MAPkinasekinase6),MKK6,1(activatorprotein21,AP21),2TLR4TLR4,/LPSTLR4[8],,LPSTLR4[9]LPS,,[10],TLR4TLR4,TLR4Haeberle[11],NF2BTLR4,TLR4,,TLR4(,AraLAM),[12]Shi[4],TLR4,TLR4TLR4LPS,,60[13],LPS,,[14],,TLR2,TLR4,TLR4,[15]3TLR4TLR4,,TLR4Oyama[16],TLR4,TLR4/LPSTLR4,TLR4LPS,LPSTLR4,[17]Pasini[18],,CD14TLR4,TLR44TLR4TLR430922009101519MedicalRecapitulate,Oct2009,Vol.15,No.19,Kumpf[14],TLR4(SNP)(Asp299Gly/Thr399lle)14.5%(9/62),TLR4SNPAmeziane[19],Asp299Gly,1Agnese[20],TLR4,[21],TLR4[22]Werner[23],TLR4LPS,TLR4,,TLR4TLR4+896+1196LPS[24],LPS,TLR24/+896TLR24/+1196,C,LPS,Werner[23]5TLR4,,,TLR4,TLR4,TLR4,,TLR4,[1]MedzhitovR,Presto2HurlburtP,JanewayCA.AhumanhomologueofthedrosophilaTollproteinsignalsactivationofadaptiveimmuni2ty[J].Nature,1997,388(3):3942397.[2]PoltorakA,HeX,SmirnovaI,etal.DefectiveLPSsignalinginC3H/HeJandC57BL/10ScCrmice:mutationsinTlr4gene[J].Science,1998,282(4):208522088.[3]PastorCM,PuginJ,KwakB,etal.RoleofToll2likereceptor4onpancreaticandpulmonaryinjuryinamicemodelofacutepancrea2titisassociatedwithendotoxemia[J].CritCareMed,2004,32(8):175921763.[4]ShiH,KokoevaMV,InouyeK,etal.TLR4linksinnateimmunityandfattyacid2inducedinsulinresistance[J].JClinInvest,2006,116(11):301523025.[5]JanewayCA,MedzhitovR.Innateimmunerecognition[J].AnnuRevImmunol,2002,20(5):1972216.[6]BacharO,AdnerM,UddmanR,etal.Toll2likereceptorstimulationinducesairwayhyper2responsivenesstobradykinin,aneffectmedi2atedbyJNKandNF2kappaBsignalingpathways[J].EurJImmu2nol,2004,34(4):119621207.[7]YanZQ.RegulationofTLR4expressionisataleabouttailarterio2sclerosis[J].ThrombVascBiol,2006,26(4):258222584.[8]GioanniniTL,WeissJP.RegulationofinteractionsofGram2nega2tivebacterialendotoxinswithmammaliancells[J].ImmunolRes,2007,39(1/3):2492260.[9]ErridgeC,Moncayo2NietoOL,MorganR,etal.Acinetobacterbau2manniilipopolysaccharidesarepotentstimulatorsofhumanmono2cyteactivationviaToll2likereceptor4signaling[J].JMedMicro2biol,2007,56(Pt2):1652171.[10]CalvanoJE,AgneseDM,UmJY,etal.Modulationofthelipopo2lysaccharidereceptorcomplex(CD14,TLR4,MD22)andtoll2likereceptor2insystemicinflammatoryresponsesyndrome2positivepa2tientswithandwithoutinfection: