β-arrestin信号转导通路在炎症性肠病发生过程中的作用机制  

Role of β-arrestins in the pathogenesis of inflammatory bowel disease

作　　者：范恒[1] 廖奕[1] 唐庆[1] 梁丽[1] 陈小艳[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院中西医结合科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2010年第29期3114-3120,共7页World Chinese Journal of Digestology

基　　金：国家自然基金面上资助项目;No;30772878~~

摘　　要：β-arrestin作为衔接蛋白参与G蛋白偶联受体(GPCR)相关信号信号通路,β-arrestin生物功能多样,能调节细胞的增殖、生存、凋亡及运动功能和基因转录过程.β-arrestin参与调节机体的炎症和免疫反应过程,抑制促炎转录因子NF-κB的基础活性,调节TLR/NF-κB信号转导通路对NF-κB的活化;参与T淋巴细胞活化,抑制CD4+T淋巴细胞凋亡,抑制NK细胞的细胞毒性作用,调节巨噬细胞的生存和功能;β-arrestin还通过调节多种趋化因子受体的脱敏、内化和信号转导过程,影响免疫细胞的趋化运动和促进中性粒细胞脱颗粒.炎症性肠病(inflammatoryboweldisease,IBD)的病因可能是多种遗传基因异常导致的机体对肠道正常菌群的过度免疫反应而形成,这种异常免疫反应被认为是IBD发生的核心因素,而β-arrestin可能通过多种途径调节其免疫反应,参与IBD肠道黏膜的炎症反应过程.因此对β-arrestin的研究必将进一步揭示IBD的发病机制,也为IBD的治疗提供了新的思路.β-arrestins,as adaptor proteins involved in G protein-coupled receptor（GPCR）-related signaling,have diverse biological functions and can regulate cell proliferation,survival,apoptosis,motility and gene transcription.β-arrestins regulate several aspects of inflammatory and immune reactions.First,they limit the basal activity of pro-inflammatory transcription factor NF-κB and regulate activation of NF-κB via the Toll-like receptors（TLR）/NF-κB signal pathway.Second,they facilitate T cell activation,suppress the apoptosis of CD4＋ T cells,inhibit NK cell-mediated cytotoxicity,and constrain factorindependent survival of macrophages.Finally,β-arrestins influence chemotaxis of immune cells and neutrophil degranulation by regulating desensitization,internalization and signal transduction of various chemokine receptors.The pathogenesis of inflammatory bowel disease（IBD） may be attributed to various genetic abnormalities that result in excessive immune response against the normal intestinal microbe flora.Abnormal immune response is considered to play a pivotal role in the development of IBD.The role of β-arrestins in regulating immune response involved in intestinal mucosal inflammation in IBD implies that they may participate in the pathogenesis of IBD.

关 键 词：Β-ARRESTIN G蛋白偶联受体 信号转导 核因子ΚB 趋化因子受体 免疫细胞 炎症性肠病 

分 类 号：R574[医药卫生—消化系统]