Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis

Background & Aims: Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are important regulators of mucosal inflammation and epithelial cell growth. To determine the role of INOS and COX-2 in Helicobacter pylori-induced tissue injury, we compared their gene expression in H. pylori-induced gastritis with that in normal gastric mucosa and in non-H. pylori gastritis. Methods: In 43 patients, we assessed H, pylori infection status, histopathology, messenger RNA (mRNA) and protein expression, and cellular localization of INOS and COX-2. Results: By reverse-transcription polymerase chain reaction (RT-PCR), antral INOS and COX-2 mRNA expression was absent to low in normal mucosa (n = 10), significantly increased in H. pylori-negative gastritis (n = 13), and even more markedly increased in H. pylori-positive gastritis (n = 20). Increased iNOS and COX-2 levels were confirmed by Northern and Western blot analysis and were both greater in the gastric antrum than in the gastric body of infected patients. Immunohistochemistry also showed increased expression of both genes in H. pylori gastritis: INOS protein was detected in epithelium, endothelium, and lamina propria inflammatory cells, and COX-2 protein localized to mononuclear and fibroblast cells in the lamina propria. Conclusions: INOS and COX-2 are induced in H. pylori-positive gastritis and thus may modulate the inflammation and alterations in epithelial cell growth that occur in this disease. Higher levels of INOS and COX-2 in H. pylori-positive vs. -negative gastritis and in gastric antrum, where bacterial density is greatest, suggest that expression of these genes is a direct response to H. pylori infection.