Study on signal transduction pathway of Helicobacter pylori-induced COX-2 expression in MKN45 cells.

Objective:To investigate the regulatory effect of p38 mitogen-activated protein kinase (p38MAPK) on expression of cyclooxygenase-2 (COX-2) in Helicobacter pylori (Hp)-infected human gastric epithelial MKN45 cells and reveal the mechanism underlying the initiation of gastric cancer induced by Hp. Methods:The expression of COX-2 mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction (RFQ-PCR) in human gastric epithelial MKN45 cells after infection with standard Hp NCTC11637. The activation of p38MAPK signaling pathway was assessed by Western blotting after Hp infection. The effect of Hp on the expression of COX-2 mRNA in MKN45 cells was observed after blocking p38MAPK signaling pathway with p38MAPK specific inhibitor SB203580. Results:The mRNA expression levels of COX-2 were 3.0-, 7.2-, 5.1-and 4.3-fold of normal value after 3, 6, 9 and 12 h Hp infection (P0.01). The mRNA expression levels of COX-2 were significantly higher than that in the control group at different time points (P0.01). Hp stimulated the p38MAPK signaling pathway at 20 min after infection and the effect reached the peak at 60 min. The expressions of COX-2 mRNA was significantly decreased after blocking the p38MAPK signaling pathway with p38MAPK specific inhibitor SB203580 (P0.01). Conclusion:Hp infection activates the p38MAPK signaling pathway. Upregulation of the expression of COX-2 mRNA in human gastric epithelial cells via p38MAPK signaling pathway may be one of the important mechanisms for the initiation of gastric cancer after Hp infection.[