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1、DEPARTMENTOFIMMUNOLOGY趨化因子及其受體(Chemokines&Chemokinesreceptors)DepartmentofImmunology,ShanghaiMedicalCollegeFudanUniversity洪曉武:021-54237093xiaowuhong@fudan.edu.cnCytokinegeneInducingstimulusCytokine-producingcellCytokineGeneactivationReceptorsignalBiologicaleffectsOverviewoftheinductiona
2、ndfunctionofCytokineIL-33:asheepinwolf'sclothing?MassimoGadinaEmail:m.g.gadina@qub.ac.ukAddress:Queen'sUniversityBelfastWhitlaMedicalBuilding97LisburnRoadBelfast?BT97BLTelephone(work):+44(0)2890972206Fig.1.Modelforthepotentialanti-inflammatoryeffectsofIL-33.ThedualeffectsofIL-33activ
3、ityaredepicted.TheprecursorformofIL-33isprocessedinthecytoplasm,possiblybytheactivityofamultiproteincaspase-1–containingcomplexknownasaninflammasome.Oncereleasedfromthecell,IL-33bindsitsreceptorcomplexatthecellsurface.Thiscomplex,whichcontainsST2and(byanalogytootherIL-1receptorfamilymem
4、bers)anas-yet-unidentifiedaccessoryreceptorrecruitstheTIRdomain–containingadaptorMyD88toitsintracellulardomainthroughahomotypicTIR-TIRinteraction.Subsequentrecruitmentoftheserine-threoninekinasesIRAK1andIRAK4anddownstreamactivationoftheE3ligaseTRAF6arethoughttodriveNF-κBandMAPKactivatio
5、nandthesubsequentproductionoftheTh2-specificcytokinesIL-4,IL-5,andIL-13.UnprocessedIL-33accumulatesinthenucleus,whereitactsasatranscriptionalrepressor.NEMO,NF-κBessentialmodifier.SIGGR,singleimmunoglobulinIL-1R-relatedmolecule.趨化因子的結(jié)構(gòu)與功能一、趨化因子概述二、趨化因子受體三、趨化因子的結(jié)構(gòu)特點四、趨化因子的生物學(xué)作用五、某些應(yīng)用趨化因子的
6、發(fā)現(xiàn)趨化因子的共性趨化因子的分類趨化因子概述趨化因子的發(fā)現(xiàn)起始期(80s中)未形成概念PF4成熟期(80s后)完整概念/分類大量趨化因子高潮期(90s中)發(fā)現(xiàn)CCR5新趨化因子及受體1992年只分為CXC類(α):4個保守的Cys,第一個和第二個Cys間隔1個氨基酸CC類(β),4個保守的Cys,第一個和第二個Cys相鄰1994年發(fā)現(xiàn)了C類趨化因子(γ)缺少第一個和第三個Cys,僅lymphotactin,主要對CD8+T淋巴細(xì)胞有趨化作用.1995年鑒定了CC類趨化因子MIP-5/HCC2、MIP-1r、Eot1和mMRP-21996年又克隆了CXC類趨化因子SDF
7、-1/PBSFCC類趨化因子HCC1和TARC1997年發(fā)現(xiàn)了第4類趨化因子CX3C類趨化因子(δ),不規(guī)則趨化因子(fractalkine)或神經(jīng)元趨化因子(neurotactin)1種,T細(xì)胞、單核細(xì)胞和中性白細(xì)胞的趨化劑。1992年,國際研討會建議把對白細(xì)胞有化學(xué)趨化作用的細(xì)胞因子(Chemoattractantcytokines)簡稱為趨化因子(chemokines),其特征和功能為:a使細(xì)胞骨架重排,引起細(xì)胞形態(tài)改變;b肌動蛋白的聚合與斷裂,引起板層足(lamellipodia)的形成和退縮(retraction);c引起整合蛋白的上調(diào)和活