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 cyclooxygenas e (COX)-2 are important regulators of mucosal inflammation and epithelial c ell growth. To determine the role of INOS and COX-2 in Helicobacter pylori- induced tissue injury, we compared their gene expression in H. pylori-induc ed gastritis with that in normal gastric mucosa and in non-H. pylori gastri tis. Methods: In 43 patients, we assessed H, pylori infection status, histo pathology, messenger RNA (mRNA) and protein expression, and cellular locali zation of INOS and COX-2. Results: By reverse-transcription polymerase chai n reaction (RT-PCR), antral INOS and COX-2 mRNA expression was absent to lo w 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 North ern and Western blot analysis and were both greater in the gastric antrum t han in the gastric body of infected patients. Immunohistochemistry also sho wed increased expression of both genes in H. pylori gastritis: INOS protein was detected in epithelium, endothelium, and lamina propria inflammatory c ells, and COX-2 protein localized to mononuclear and fibroblast cells in th e lamina propria. Conclusions: INOS and COX-2 are induced in H. pylori-posi tive gastritis and thus may modulate the inflammation and alterations in ep ithelial 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.