Cross-talk between inducible nitric oxide synthase and cyclooxygenase in Helicobacter-pylori-induced gastritis.

OBJECTIVES The present study examined the cross-talk between prostanoids and nitric oxide (NO) in human gastric biopsies during Helicobacter pylori infection. SUBJECTS AND METHODS A pool of 1 or 2 biopsies per patient (11 H. pylori positive and 9 H. pylori negative) were incubated in the medium with/without drugs, 1400W and NS-398, inhibitors of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Levels of NO and prostaglandin E(2) (PGE(2)), predominant products of activity of NOS and COX enzymes, were measured in the medium whereas the expressions of iNOS and COX protein, examined by Western blotting, were measured in the biopsies. RESULTS The 11 patients with H. pylori infection showed a marked expression of COX-2 and iNOS proteins and high levels of PGE(2) and NO, as a consequence of iNOS and COX-2 activation, while proteins were absent and the level of nitrite and PGE(2) was low in the 9 noninfected patients. The COX-2 inhibitor decreased both NO and PGE(2). The iNOS-specific inhibitor decreased NO but did not have any effect on the increase in gastric mucosal PGE(2). Both inhibitors had no effect on the protein level of these two enzymes. CONCLUSIONS The data showed that COX-2 inhibitor might modulate the iNOS pathway, suggesting that COX-2 activity and/or its products may be related to the functional activation of iNOS but not to the expression of iNOS protein.