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1、药学学报ActaPharmaceuticaSinica2016,51(10):1505−1512·1505··综述·NLRP3炎症小体调控机制研究进展*刘雯,郭文洁,徐强,孙洋(南京大学生命科学学院,医药生物技术国家重点实验室,江苏南京210023)摘要:炎症小体活化是由多蛋白复合物组装信号介导的炎症相关的半胱氨酸天冬氨酸特异蛋白酶(caspase)活化以及白细胞介素-1(interleukin-1β,IL-1β)、白细胞介素-18(interleukin-18,IL-18)等炎症因子的成熟过程。其中NOD(nucleotidebindin
2、goligomerizationdomain)样受体家族3(NOD-likereceptors,NLRP3)炎症小体是目前研究最透彻的炎症小体类型,它参与了人类众多疾病的发生发展。因此靶向NLRP3炎症小体已经成为相关疾病治疗药物开发的热点。本综述总结了近5年来关于NLRP3炎症小体的研究进展,包括NLRP3priming阶段的调控、蛋白复合物组装的调控、内源性代谢物质及亚细胞器对NLRP3的活化调节及小分子抑制剂的研究。对NLRP3调控机制的深入认识将有助于新药物靶标发现和治疗药物的开发。关键词:炎性疾病;NLRP3炎症小体;白介素-1β
3、;调控中图分类号:R965文献标识码:A文章编号:0513-4870(2016)10-1505-08AdvancesinmechanismsforNLRP3inflammasomesregulation*LIUWen,GUOWen-jie,XUQiang,SUNYang(StateKeyLaboratoryofPharmaceuticalBiotechnology,SchoolofLifeSciences,NanjingUniversity,Nanjing210023,China)Abstract:Activationofinflammas
4、omesinvolvesmulti-proteinassemblyandactivationofinflammatorycaspaseandmaturationofpro-inflammatorycytokinesinterleukin-1β(IL-1β)andinterleukin-18(IL-18).Amongthosetypesofinflammasomes,NOD(nucleotidebindingoligomerizationdomain)-likereceptors(NLRP3)isthemoststudiedinflammas
5、omewhichinvolvesinamountofhumaninflammatoryandautoimmunediseases.Therefore,targetingonNLRP3inflammasomehasbeenoneofthepromisingmethodsfortreatmentofdiseases.Inthisreview,wefocusedonthestudiesinthelatestfiveyearsonthemechanismsofNLRP3inflammasomeregulationwhichmainlyincludi
6、ngNLRP3priming,threeproteincomplexassemblyandregulationofNLRP3inflammasomeactivationbyendogenousmetaboliccompounds,ironflux,subcellularstructure,othertypesofcellsandsmallmolecularcompounds.BetterunderstandingofNLRP3inflammasomewillbebenefitforpotentialdrugtargetandtreatmen
7、tofNLRP3inflammasome-associateddiseases.Keywords:inflammatarydisease;NLRP3inflammasome;interleukin-1β;regulation当机体受到外来微生物感染(pathogen-associated(danger-associatedmolecularpatterns,DAMPs)刺激时,molecularpatterns,PAMPs)或来自本身的损伤信号便会启动先天性免疫系统通过其表面的模式识别受体或感应系统激活炎症反应,促进typeIinterfe
8、rons(interferon-α和interferon-β)或炎症因子IL-1β、IL-18收稿日期:2016-04-22;修回日期:2016-05-25.基金项目:国家自然科
