Effects of cyclooxygenase-1 and -2 gene disruption on Helicobacter pylori-induced gastric inflammation

Background. Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. Methods. Wild-type (WT), COX-1 and COX-2 heterozygous ( COX-1(+/-) and COX- 2(+/-)), and homozygous COX- deficient (COX-1(-/-) and COX-2(-/-)) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX- deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. Results. COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX- deficient mice, whereas cell proliferation was increased in WT and COX- 1 deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E-2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B-4 and LTC4 levels were increased to a similar extent in infected WT and COX- deficient mice. Conclusions. COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX- 2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.