幽门螺杆菌及其相关细胞因子对胃上皮细胞凋亡的调控及相关机制  

Effects of Helicobacter pylori and Helicobacter pylori-related cytokines on apoptosis of gastric epithelial cells and mechanisms thereof

作　　者：郭涛[1] 钱家鸣[1] 张建中[2] 李晓波[3] 赵雩卿 

机构地区：[1]100730中国医学科学院 [2]中国疾病预防控制中心传染病预防控制所传染病诊断室 [3]北京大学人民医院肝病研究所

出　　处：《中华医学杂志》2006年第38期2670-2673,共4页National Medical Journal of China

基　　金：国家自然科学基金(30270600)

摘　　要：目的研究幽门螺杆菌(Hp)及其相关细胞因子对胃上皮细胞凋亡的影响,以探讨 Hp的致病机理。方法以人胃永生化上皮细胞株(GES-1)和人胃癌细胞株(AGS)作为研究对象。流式细胞术检测 Hp 毒力菌株(NCTC 11637)单独及分别联合 Hp 相关细胞因子[白细胞介素(IL)-1β、IL-8及 IL-10]对两种细胞系凋亡的影响;检测 IL-1β、IL-8及 IL-10对外源性 Fas 配体(FasL)诱导的两种细胞系凋亡的影响。逆转录-聚合酶链反应检测 Hp 及其相关细胞因子(IL-1β、IL-8及 IL-10)对两种细胞系 Fas mRNA 基础表达水平的影响。结果(1)Hp 能诱导 GES-1和 AGS 细胞凋亡增加113.0％和47.0％(均 P<0.05);IL-1β、IL-10能抑制 Hp 诱导的 GES-1(29.6％、25.8％)和 AGS(19.7％、21.1％)细胞凋亡(均 P<0.05);IL-8能增强 Hp 诱导的 GES-1细胞凋亡(19.9％,P<0.05)。(2)Hp能上调 GES-1和 AGS 细胞 Fas mRNA 基础表达水平(89.0％和36.0％,P<0.05);IL-1β、IL-10对两种细胞 Fas mRNA 基础表达无显著影响(P>0.05);IL-8能上调 GES-1(33.0％)细胞 Fas mRNA 基础表达(P<0.05)。(3)IL-1β、IL-10能抑制 FasL 诱导的 GES-1(30.3％、32.5％)和 AGS(44.2％、51.5％)细胞凋亡(P<0.05);IL-8能增强 FasL 诱导的 GES-1细胞凋亡(100％,P<0.05)。结论Hp 可通过上调 Fas 受体表达直接介导胃上皮细胞凋亡。Hp 相关细胞因子 IL-8可能通过上调 Fas 受体表达来增强 Hp 诱导的胃上皮细胞凋亡;IL-1β和 IL-10可能通过其他机制来抑制 Hp 诱导的胃上皮细胞凋亡。Objective To investigate the influence of Helicobacter pylon （H. pylori） and H. pylori-related cytokines on the apoptosis of gastric epithelial cells and mechanisms thereof. Methods （ 1 ） Human gastric cancer cells of the line AGS and human gastric epithelial cells of the line GES-1 were cultured as control group, or incubated with H. pylori alone or H. pylori in combination with exogenous cytokines： interleukin （IL） -1β, IL-8, or IL-10 for 24 hours. Then flow cytometry （FCM） was used to determine the rate of apoptosis. （2） The GES-1 and AGS ceils were incubated with H. pylori for 24 hours and exogenous cytokines for 2 hours respectively. Then RT-PCR was used to examine the level of Fas mRNA expression. （3） Another GES-1 and AGS cells were cultured as control group, or incubated with FasL alone or FasL ＋ exogenous cytokine for 2 hours （incubated with IL-1β, IL-8, or IL-10 for 2 hours before being added with FasL）. Then FCM was used to detect the apoptosis rate. Results （ 1 ） In comparison to the apoptosis level of control group, H. pylori induced an increase in the apoptosis rate of GES-1 and AGS cells by 113.0% and 47.0% respectively （ both P 〈 0. 05 ）. The H. pylori-induced apoptosis rates of GES-1 cells （ by 29. 6% or25. 8% ） and AGS ceils （by 19.7% or 21.1% ） were reduced by IL-1β or IL-10 （ all P 〈0. 05）. IL-8 increased the H. pylori-induced apoptosis level of GES-1 cells by 19. 9% （P 〈 0. 05 ）. （2） In the baseline status, both GES-1 and AGS cells showed Fas mRNA expression. The Fas mRNA expressions of the GES-1 and AGS cells incubated with H. pylori were increased by 89. 0% and 36.0% respectively （ both P 〈 0.05 ）in comparison to that of the control group. IL-1 β and IL-10 had no significant effect on the basal Fas mRNA expressions in both GES-1 and AGS cells （ all P 〉 0. 05 ）. IL-8 up-regulated the basal Fas mRNA expression level of the GES-1 cells by 33.0% （P 〈0.05）. （3） IL-Iβ and IL-10 inhibited the FasL-induced

关 键 词：螺杆菌 幽门 细胞因子 凋亡 FAS受体 

分 类 号：R573[医药卫生—消化系统]