Involvement of Ras and AP-1 in Helicobacter pylori-induced expression of COX-2 and iNOS in gastric epithelial AGS cells.
Authors
Seong Bok Jang ; Yoon Jung Lee ; Lay Ahyoung Lim ; Kyung-Mi Park ; Bong-Ju Kwon ; Jong Soo Woo ; Yong-IL Kim ; Min Soo Park ; Kyung Hwan Kim ; Kyungsoo Park
Citation
DIGESTIVE DISEASES AND SCIENCES, Vol.55(4) : 988-996, 2010
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.