诱导胃上皮细胞白细胞介素-8分泌的幽门螺杆菌基因型

摘要

目的分析临床分离的幽门螺杆菌的cag致病岛的差异和不同激酶抑制剂对幽门螺杆菌诱导人胃上皮细胞白细胞介素-8(IL-8)分泌的影响。方法分别用临床分离的不同基因型的cagA+cagE+、cagA+ cagE-、cagA-cagE+、cagA-cagE- 幽门螺杆菌与人胃上皮细胞MGC-803共同培养，IL-8分泌用酶联免疫吸附试验进行检测，比较蛋白激酶A、C、G和蛋白酪氨酸激酶的抑制剂对幽门螺杆菌诱导胃上皮细胞IL-8分泌的影响。结果 cagA+cagE+基因型幽门螺杆菌显著增加了胃上皮细胞IL-8的分泌，cagA+ cagE- 、cagA-cagE+幽门螺杆菌作用次之，而cagA-cagE-幽门螺杆菌不能增加胃上皮细胞IL-8的分泌。蛋白激酶A、C、G的抑制剂不能阻断幽门螺杆菌增加胃上皮细胞IL-8的分泌，而蛋白酪氨酸激酶的抑制剂阻断了幽门螺杆菌增加胃上皮细胞IL-8的分泌。结论cagA+cagE+基因型幽门螺杆菌显著增加了胃上皮细胞IL-8的分泌并且依赖于蛋白酪氨酸激酶的磷酸化。%Objective　To study the effect of different cag pathogenicity island in Helicobacter pylori (Hp) from Chinese patients and various kinase inhibitors on Hp induced interleukin-8 (IL-8) secretion in Chinese gastric epithelial cells.Method　Chinese gastric epithelial cells(MGC-803) were cocultured with Chinese clinical cagA+cagE+,cagA+cagE-,cagA-cagE+,cagA-cagE- Hp in vitro,respectively.At the end of culture,IL-8 protein secretion was assayed by ELISA.The effect of the inhibitor of protein kinase A(PKA),C,G,protein tyrosine kinase(PTK) was analyzed on IL-8 protein secretion in gastric epithelial cells by Hp stimulation.Results　cagA+cagE+Hp induced IL-8 protein secretion higher than cagA+ cagE- or cagA-cagE+ Hp,but cagA-cagE-Hp didn′t increase IL-8 protein secretion in gastric epithelial cells.Further studies with gastric epithelial cell showed that IL-8 protein secretion induced by cagA+cagE+Hp was blocked by the PTK inhibitor herbimycin A but not by PKA inhibitor H7,PKC inhibitor calphostin C,and PKG inhibitor KT5823.Conclusion　cagA+cagE+Hp significantly increases IL-8 protein secretion and it depends on PTK activation in gastric epithelial cells.