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  • 简介:<正>Fasligand(FasL)wasfirstdescribedfunctionallyasaninduciblecellsurfacemoleculeusedbycytotoxicTcellstoinduceapoptoticcelldeathintumorcellsandactivatedlymphocytes.WiththeidentificationofFasastheIprgeneproduct,FasLbecamerecognizedasamoleculeinvolvedindown-regulationoftheimmunesystem.WhileFasLcanbeusedtoefficientlykillFas-expressingtumorcellsaswellasactivatedTandBlymphocytesinvitro,attemptstouseFasLtherapeuticallytotreatcancerortopreventtransplant

  • 标签: FAS配体 免疫调节作用 毒性 基因治疗 应用
  • 简介:ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.

  • 标签: B淋巴细胞 FAS介导 细胞凋亡 FAIM FLIP CD40
  • 简介:<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson

  • 标签: 初级B淋巴细胞 Fas介导细胞凋亡 耐受性 信号转导
  • 简介:Fas/CD95表面受体调停各种各样的房间的快速的死亡打字,包括有为触发autoimmunity的潜力的autoreactiveT房间。这里,我们表明那的船边交货的现在的新奇方面定义一种“社会”的尺寸到导致受体的apoptosis。船边交货刺激很快导致在附近的T房间之间的广泛的膜nanotube形成。这极其依赖于RhoGTPases然而并非在caspase激活上。包括活跃caspases的膜和cytosolic元素的双向转移能被观察经由这些nanotubes发生。Nanotube形成和死亡信号的细胞间的交换在从有在船边交货受体的自体免疫的lymphoproliferative症候群harbouring变化的病人的T淋巴细胞是有缺点的。我们断定调停nanotube的交换组成扩充在附近的T房间之间发信号的死亡的繁殖的细胞间的通讯的一种新奇形式。

  • 标签: T淋巴细胞 碳纳米管 细胞信号 FAS 死亡 交流
  • 简介:Apoptosisplaysanimportantroleinembryonicdevelopment,tissueremodeling,immuneregulationandtumorregression.Twogroupsofmolecules(Bcl-2familyand“Deathfactor”family)areinvolvedinregulatingapoptosis.InordertoknowabouttheeffectofBcl-2onapoptosisinducedbyFas,atypicalmemberof“Deathfactor”family,thetransfectionexperimentswithexpressionvectorspcDNA3-flandpcDNA3-bcl-2wereperformedinBEL-7404cells,ahumanhepatocellularcarcinomacelllinewhichexpressesendogenousFas,butnotFasLandBcl-2.ThedatashowedthattheexpressionofFasLinpcDNA3-fltransfectedhepatomacellsobviouslyinducedtheapoptosisofthecells.However,theoverexpressionofBcl-2inpcDNA3-bcl-2transfected7404/b-16cellscounteractedpcDNA3-fltransienttransfectionmediatedapoptosis.FurtherstudybycotransfectionexperimentsindicatedthatBidbutnotBax(bothwerepro-apoptoticproteinsofBcl-2family)blockedtheinhibitoryeffectofBcl-2onFas-mediatedapoptosis.TheseresultssuggestedthatFas-mediatedapoptosisinhumanhepatomacellsispossiblyregulatedbyBcl-2familyproteinsviamitochondriapathway.

  • 标签: 人肝细胞瘤 BEL-7404细胞 FASL Bcl-2 细胞凋亡 表达
  • 简介:目的:研究双歧杆菌三联活菌片对溃疡性结肠炎患者免疫功能及Fas/FasL表达的影响.方法:选取2014年7月至2015年6月本院收治的84例溃疡性结肠炎患者,根据患者入院顺序分为观察组(42例)和对照组(42例)两组.对照组采取美沙拉秦肠溶片进行治疗,观察组在此基础上结合双歧杆菌三联活菌片进行治疗.分析两组患者治疗前和治疗2个月后炎症因子水平、T细胞亚群以及Fas/FasL表达情况,并比较两组患者的临床疗效.结果:观察组总的有效率显著高于对照组(P<0.05).治疗后,观察组的血清白介素-1(IL-1)、白介素-6(IL-6)、白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平显著低于对照组(P<0.05),CD4+、CD4+/CD8+T细胞亚群显著高于对照组,CD8+、Fas/FasL表达显著低于对照组,差异均有统计学意义(P<0.05).结论:使用双歧杆菌三联活菌片治疗溃疡性结肠炎患者能改善患者的免疫功能及Fas/Fasl表达,减轻炎症反应,临床效果良好.

  • 标签: 双歧杆菌三联活菌片 溃疡性结肠炎 免疫功能