幽门螺杆菌依赖丝裂原活化蛋白激酶信号通路诱导SGC7901细胞表达分泌白细胞介素-8

Helicobacter pylori Inducing Interleukin-8 Expression and Production in SGC7901 Cells through Mitogen-activ-ated Protein Kinase Signal Pathway

背景:已知前炎症细胞因子白细胞介素(IL)鄄8在慢性活动性胃炎、消化性溃疡等幽门螺杆菌(H.pylori)感染相关疾病的发生、发展中起重要作用,但H.pylori诱导胃上皮细胞表达、分泌IL鄄8的分子机制尚不明确。目的:通过体外实验了解H.pylori对人胃癌细胞株SGC7901表达、分泌IL鄄8的影响,探讨p38丝裂原活化蛋白激酶(MAPK)信号通路在H.pylori诱导SGC7901细胞IL鄄8mRNA表达和IL鄄8蛋白分泌中的作用。方法:SGC7901细胞经p38MAPK特异性抑制剂SB203580预作用2h,再加入H.pylori标准菌株CCUG17874共培养。采用逆转录聚合酶链反应(RT鄄PCR)检测IL鄄8mRNA的表达,采用酶联免疫吸附测定(ELISA)检测IL鄄8蛋白的分泌,观察SB203580对H.pylori诱导SGC7901细胞表达、分泌IL鄄8的影响。结果:H.pylori能诱导SGC7901细胞表达、分泌IL鄄8。SB203580能以剂量依赖的方式抑制H.pylori诱导的SGC7901细胞IL鄄8蛋白分泌,经终浓度为0.3、1、3和10μmol/L的SB203580预作用2h,SGC7901细胞的IL鄄8蛋白分泌与未经SB203580预作用组相比分别减少了26%、51%、64%和73%(P<0.05);SB203580也能使H.pylori诱导的IL鄄8mRNA表达显著减弱。结论:H.pylori能诱导胃上皮细胞表达、分泌IL鄄8,该作用在一定程度上依赖于MAPK信号通路。

It is known that proinflammatory cytokine interleukin (IL)-8 plays a vital role in the development and progression of Helicobacter pylori (H. pylori) infection-associated diseases such as chronic active gastritis and peptic ulcer, but the molecular mechanism of inducing IL-8 expression and production in gastric epithelial cells remains unclear. Aims: To study the effect of on the expression and production of IL-8 in human gastric cancer cell line SGC7901, and to investigate the role of p38 mitogen-activated protein kinase (MAPK) signal pathway in IL-8 mRNA expression and IL-8 protein secretion from SGC7901 cells induced by H. pylori in vitro. Methods: The standard H. pylori strain CCUG17874 was co-cultured with SGC7901 cells, which were prior treated with a specific p38 MAPK inhibitor SB203580 for 2 hours. IL-8 mRNA expression was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and IL-8 protein secretion was determined by enzyme-linked immunosorbent assay (ELISA). Then the effect of SB203580 on IL-8 expression and production in SGC7901 cells induced by H. pylori was observed. Results: The expression and production of IL-8 in SGC7901 cells could be induced by H. pylori. SB203580 could inhibit the IL-8 protein secretion from SGC7901 cells induced by H. pylori in a dose-dependent manner, significant inhibition (26%, 51%, 64% and 73%) was observed in SGC7901 cells pretreated with 0.3, 1, 3 and 10 μmol/L SB203580 respectively, for 2 hours, as compared with those without SB203580 pretreatment (P<0.05). SB203580 also inhibited the expression of IL-8 mRNA significantly induced by H. pylori. Conclusions: The expression and production of IL-8 in gastric epithelial cells can be induced by H. pylori, which is at least in part dependent on MAPK signal pathway.