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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：Coactivatorsandcorepressorsregulatetranscriptionbycontrollinginteractionsbetweensequence-specifictranscriptionfactors,thebasaltranscriptionalmachineryandthechromatinenvironment,Thisreviewconsidertheaccessofnuclearandsteroidreceptorstochromatin,theiruseofcorepressorsandcoactivatorstomodifychromatinstructureandtheimplicationsfortranscriptionalcontrol.Theassemblyofspecificnucleoproteinarchitecturesandtargetedhistonemodificationemergeascentralcontrollingelementsforgeneexpression.

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

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简介：在病原体识别的像使用费的受体(TLR)的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的TLR的功能的调查刚开始了。以前，我们和其它表明了那碎裂的hyaluronan(哈)在织物损害期间积累。CD44被要求在织物损害期间清除HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求TLR2和TLR4刺激老鼠巨噬细胞生产煽动性的chemokines和cytokines。在一个非传染的肺损害模型，在TLR2和TLR4缺乏的老鼠显示出煽动性的房间的损害transepithelial迁居，增加的织物损害，提高的肺上皮的房间apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和apoptosis的保护的老鼠，部分地通过NF-kappaB的TLR依赖的基础激活。在TLR2和TLR4的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害HA-TLR相互作用。这些研究识别那个主机矩阵部件哈并且TLR相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006)16：693-701。做i：10.1038/sj.cr.7310085；出版联机2006年8月8日。

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

简介：Two-armedneutralanionreceptors(4,5),calix[4]arenesbeatingthioureaandamidebindingsites,werepreparedandexaminedtheiranion-bindingabilitybytheUV-visspectra.Theresultsofnon-linearcurvefittingandJobplotindicatethat4or5forms1：1stoichiometrycomplexwithfluoridebyhydrogenbondinginteractions.Receptors4and5haveanexcellentselectivityforfluoridebuthavenobindingabilitywithacetate,dihydrogenphosphateandthehalogenanions(Cl^-,Br^-,I^-).

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

简介：AcomputationalsystemforthepredictionandclassificationofhumanG-proteincoupledreceptors(GPCRs)hasbeendevelopedbasedonthesupportvectormachine(SVM)methodandproteinsequenceinformation.ThefeaturevectorsusedtodeveloptheSVMpredictionmodelsconsistofstatisticallysignificantfeaturesselectedfromsingleaminoacid,dipeptide,andtripeptidecompositionsofproteinsequences.Furthermore,thelengthdistributiondifferencebetweenGPCRsandnon-GPCRshasalsobeenexploitedtoimprovethepredictionperformance.ThetestingresultswithannotatedhumanproteinsequencesdemonstratethatthissystemcangetgoodperformanceforbothpredictionandclassificationofhumanGPCRs.

简介：G-proteincoupledreceptors(GPCRs)areaclassofseven-helixtransmembraneproteinsthathavebeenusedinbioinformaticsasthetargetstofacilitatedrugdiscoveryforhumandiseases.AlthoughthousandsofGPCRsequenceshavebeencollected,theligandspecificityofmanyGPCRsisstillunknownandonlyonecrystalstructureoftherhodopsin-likefamilyhasbeensolved.Therefore,identifyingGPCRtypesonlyfromsequencedatahasbecomeanimportantresearchissue.Inthisstudy,anoveltechniqueforidentifyingGPCRtypesbasedontheweightedLevenshteindistancebetweentworeceptorsequencesandthenearestneighbormethod(NNM)isintroduced,whichcandealwithreceptorsequenceswithdifferentlengthsdirectly.Inourexperimentsforclassifyingfourclasses(acetylcholine,adrenoceptor,dopamine,andserotonin)oftherhodopsin-likefamilyofGPCRs,theerrorratesfromtheleave-one-outprocedureandtheleave-half-outprocedurewere0.62%and1.24%,respectively.Theseresultsarepriortothoseofthecovariantdiscriminantalgorithm,thesupportvectormachinemethod,andtheNNMwithEuclideandistance.

简介：G-proteincoupledreceptors(GPCRs)representoneofthemostimportantclassesofdrugtargetsforpharmaceuticalindustryandplayimportantrolesincellularsignaltransduction.PredictingthecouplingspecificityofGPCRstoG-proteinsisvitalforfurtherunderstandingthemechanismofsignaltransductionandthefunctionofthereceptorswithinacell,whichcanprovidenewcluesforpharmaceuticalresearchanddevelopment.Inthisstudy,thefeaturesofaminoacidcompositionsandphysiochemicalpropertiesofthefull-lengthGPCRsequenceshavebeenanalyzedandextracted.Basedonthesefeatures,classifiershavebeendevelopedtopredictthecouplingspecificityofGPCRstoG-proteinsusingsupportvectormachines.Thetestingresultsshowthatthismethodcouldobtainbetterpredictionaccuracy.

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.