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简介：Modulationbybalancingactivatingandinhibitoryreceptorsconstitutesanimportantmechanismforregulatingimmuneresponses.Cellsthatareactivatedfollowingligationofreceptorsbearingimmunoreceptortyrosine-basedactivationmotifs(ITAMs)canbenegativelyregulatedbyotherreceptorsbearingimmunoreceptortyrosine-basedinhibitionmotifs(ITIMs).Humanmastcells(MCs)arethemajoreffectorcellsoftypeIhypersensitivityandimportantparticipantsinanumberofdiseaseprocesses.Antigen-mediatedaggregationofIgEboundtoitshigh-affinityreceptoronMCsinitiatesacomplexseriesofbiochemicaleventsleadingtoMCactivation.WithgreatdetaileddescriptionandanalysisofseveralinhibitoryreceptorsonhumanMCs,acentralparadigmofnegativeregulationofhumanMCactivationbythesereceptorshasemerged.Cellular&MolecularImmunology.2004;1(6):408-415.

简介：Hormonesandtheirreceptorsregulatecellgrowth,differentiationandapoptosisandalsoplayimportantrolesinimmunefunction.Recentstudiesonthesubfamilyoftheorphannuclearreceptorsknownasretinoid-acidrelatedorphanreceptors(ROR)haveshedimportantinsightsontherolesofthisgroupofnuclearproteinsinthedevelopmentandfunctionoftheimmunesystem.RORαregulatesinflammatorycytokineproductioninbothinnateandadaptiveimmunesystemwhileRORγregulatesthenormaldevelopmentofTlymphocyterepertoireandsecondarylymphoidorgans.Cellular&MolecularImmunology.2004;1(6):401-407.

简介：ＡＲｅｓｅａｒｃｈＩｎｓｔｉｔｕｔｅｏｆＳｕｒｇｅｒｙ，ＤａｐｉｎｇＨｏｓｐｉｔａｌ，ＴｈｉｒｄＭｉｌｉｔａｒｙＭｅｄｉｃａｌＵｎｉｖｅｒｓｉｔｙ，Ｃｈｏｎｇｑｉｎｇ４０００４２，Ｃｈｉｎａ（ＬｉｕＬＭ，ＣｈｅｎＨＳ，ＨｕＤＹ，ＬｕＲＱ，ＣｈｅｎＹ...

简介：Thenuclearreceptorsuperfamilyandthetranscriptionalfactorsassociatedwithcytokinesareinherentlydifferentfamiliesofsignalingmoleculesandactivategenetranscriptionbybindingtotheirrespectiveresponsiveelement.However,ithasbecomeincreasinglyclearfromourworksandothersthatnuclearreceptorsareimportantregulatorsofcytokineproductionandfunctionthroughcomplexandvariedinteractionsbetweenthesedistincttranscriptionalfactors.Thisreviewprovidesageneraloverviewofthemechanismofactionofnuclearreceptorsandtheirtranscriptionalcrosstalkwithtranscriptionalfactorsassociatedwithcytokinetransductionpathways.Oneofthemostimportantmechanisticaspectsisproteintoproteininteractionthroughadirectorco-regulator-mediatedindirectmanner.Suchcrosstalkiscruciallyinvolvedinphysiologicalandtherapeuticrolesofnuclearreceptorsandtheirligandsinimmunity,inflammationandcytokine-relatedtumors.Cellular&MolecularImmunology.2004;1(6):416-424.

简介：Arachidonicacid-metabolizingenzyme5-lipoxygenase(5-LOX)producespro-inflammatorymediators:leukotrienes(includingcysteinylleukotrienes,CysLTs).5-LOXandCysLTsareinvolvedinthepathophysiologicalprocessafterbraininjury,andtheactionsofCysLTsaremediatedviaactivationoftheirreceptors,CysLT1andCysLT2.Wehaverecentlyreportedtheexpressionsof5-LOX,CysLT1andCysLT2inhumanbrainswithtraumaticinjuryandtumors,andshort-termneuroprotectiveeffectsofCys-LT1antagonistsinstrokemodelsofratsandmice.

简介：Objective:ToinvestigatetheeffectofsubstanceP(SP)ongeneexpressionoftransforminggrowthfactorβ-1(TGFβ-1),transforminggrowthfactorreceptor-1(TGFR-1)andtransforminggrowthfactorreceptor-2(TGFR-2)infibroblastsculturedinvitrofromrat'sgranulationtissues.Methods:Thefibroblastsfromthegranulationtissuesintheskeletalmuscleofrat'shindlimbsinjuredbyformaldehydewereculturedinvitro.Whendifferentconcentrations(10-9-10-5mol/L)ofSPwereaddedintotheculturemedium,thechangesofgeneexpressionofTGFβ-1,TGFR-1andTGFR-2intheculturedfibroblastswereobservedwithreversetranscriptionpolymerasechainreactionatdifferentintervals(0,3,6,12and24hoursafterincubation).Results:ThegeneexpressionofTGFβ-1,TGFR-1andTGFR-2inthefibroblastsculturedfromrat'sgranulationtissueswasup-regulatedbySP.ThepeaklevelofthemRNAexpressionwasfoundat10-8mol/LSPandtheup-regulationeffectwasnotfoundat10-5mol/Land10-6mol/L.ThepeaklevelsofgeneexpressionofTGFβ-1,TGFR-1andTGFR-2inthefibroblaststreatedwithSPwereachievedat6and12hours,respectively.Conclusions:SPhasup-regulationeffectonthegeneexpressionofTGFβ-1,TGFR-1andTGFR-2infibroblastsfromrat'sgranulationtissuesinvitro,andtheeffectisrelatedtodifferentstimulatingconcentrationsofSP.Itmaybeconcernedwithproliferationanddifferentiationoffibroblastsandformationofscartissuesduringwoundhealing.

简介：Chemokinesbelongtoalargefamilyofinflammatorycytokinesresponsibleformigrationandaccumulationofleukocytesatinflammatorysites.Overthepastdecade,accumulatingevidenceindicatedacrucialroleforchemokinesandchemokinereceptorsinthepathophysiologyofrheumatoidarthritis(RA).RAisachronicautoimmunediseaseinwhichthesynovialtissueisheavilyinfiltratedbyleukocytes.Chemokinesplayanimportantroleintheinfiltration,localization,retentionofinfiltratingleukocytesandgenerationofectopicgerminalcentersintheinflamedsynovium.RecentevidencealsosuggeststhatidentificationofinhibitorsdirectlytargetingchemokinesortheirreceptorsmayprovideanoveltherapeuticstrategyinRA.TraditionalChinesemedicinals(TCMs)havealonghistoryinthetreatmentofinflammatoryjointdisease.ThebasisfortheclinicalbenefitsofTCMremainslargelyunclear.Ourstudieshaveledtotheidentificationofnumerousnovelchemokine/chemokinereceptorinhibitorspresentinanti-inflammatoryTCMs.Alloftheseinhibitorswerepreviouslyreportedbyotherresearcherstohaveanti-arthriticeffect,whichmaybeattributable,atleastinpart,totheirinhibitoryeffectonchemokineand/orchemokinereceptor.Therefore,identificationofagentscapableoftargetingchemokine/chemokinereceptorinteractionshassuggestedamechanismofactionforseveralTCMcomponentsandprovidedameansofidentifyingadditionalanti-RATCM.Thus,thisapproachmayleadtothediscoveryofnewinhibitorsofchemokinesorchemokinereceptorsthatcanbeusedtotreatdiseasesassociatedwithinappropriatelyoveractivechemokinemediatedinflammatoryreactions.Cellular&MolecularImmunology.2004;1(5):336-342.