Involvement of Ras and AP-1 in Helicobacter pylori-Induced Expression of COX-2 and iNOS in Gastric Epithelial AGS Cells
Involvement of Ras and AP-1 in Helicobacter pylori-Induced Expression of COX-2 and iNOS in Gastric Epithelial AGS Cells
复制标题
DOI：
10.1007/s10620-009-0828-y
复制
发表时间：
2010-04-01
影响因子：
3.1
通讯作者：
Kim, Hyeyoung
中科院分区：
文献类型：
--
作者：
Cho, Soon Ok;Lim, Joo Weon;Kim, Hyeyoung
幽门螺杆菌（H. pylori）是慢性胃炎、消化性溃疡和胃癌的重要危险因素。幽门螺杆菌分离株的遗传差异在感染的临床结果中发挥着重要作用。包括环氧合酶-2 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 在内的炎症基因与幽门螺杆菌胃炎有关。转录因子AP-1由c-Fos和c-Jun组成，介导炎症和癌变。 Ras 在多种细胞中充当 AP-1 激活的调节者。我们研究了韩国分离株（HP99）（一种cagA（+）、vacA（+）菌株）中的幽门螺杆菌是否诱导c-Fos和c-Jun的表达以激活AP-1以诱导COX-2和iNOS，以及HP99诱导的COX-2和iNOS的表达是否由Ras和AP-1介导，通过胃上皮AGS细胞中c-Fos和c-Jun的表达来确定，使用用 Ras (ras N-17) 和 c-Jun (TAM-67) 突变基因转染。结果，HP99诱导AGS细胞中c-Fos和c-Jun的表达以及COX-2和iNOS的表达。 Ras 或 c-Jun 突变基因转染可抑制 HP99 诱导的 AGS 细胞中 COX-2 和 iNOS 的表达。总之，韩国分离株中的幽门螺杆菌通过 AP-1 激活诱导 COX-2 和 iNOS 的表达，这可能是由 Ras 以及胃上皮细胞中 c-Fos 和 c-Jun 的表达介导的。
Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. The genetic differences of H. pylori isolates play a role in the clinical outcome of the infection. Inflammatory genes including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in H. pylori gastritis. Transcription factor AP-1 is composed of c-Fos and c-Jun and mediates inflammation and carcinogenesis. Ras acts as a regulator for AP-1 activation in various cells. We investigated whether H. pylori in a Korean isolate (HP99), a cagA(+), vacA(+) strain, induces the expression of c-Fos and c-Jun for AP-1 activation to induce COX-2 and iNOS and whether HP99-induced expressions of COX-2 and iNOS are mediated by Ras and AP-1, determined by the expressions of c-Fos and c-Jun, in gastric epithelial AGS cells, using transfection with mutant genes for Ras (ras N-17) and c-Jun (TAM-67). As a result, HP99 induced the expression of c-Fos and c-Jun and the expressions of COX-2 and iNOS in AGS cells. Transfection with mutant genes for Ras or c-Jun suppressed HP99-induced expressions of COX-2 and iNOS in AGS cells. In conclusion, H. pylori in a Korean isolate induces the expression of COX-2 and iNOS via AP-1 activation, which may be mediated by Ras and the expression of c-Fos and c-Jun in gastric epithelial cells.