Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa.

Abstract Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE 2 and PGI 2 ) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H . pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa. Prostaglandin (PGE 2 ) and prostacyclin (PGI 2 ) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H . pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry. In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE 2 and PGI 2 were seen in patients infected with H. pylori (191±30 and 245±88 ng/mg protein, respectively) compared with non-infected patients (77±17 and 120±36 ng/mg protein, respectively). There was significant inhibition of PGE 2 and PGI 2 with aspirin in both H. pylori infected (28±6.6 and 53±43 ng/mg, respectively) and in non-infected patients (16±7 and 12.5±3.5 ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2. Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp -infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE 2 in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.