The effect of NSAIDs and a COX-2 specific inhibitor on Helicobacter pylori-induced PGE(2) and HGF in human gastric fibroblasts

Background: There is compelling evidence for the pivotal role of Helicobact er pylori in the pathogenesis of gastrointestinal ulcer disease. However, d espite the bacterium's toxicity, the majority of H. pylori infections are n ot accompanied by gastric ulcers. This implies the existence of a host mech anism offsetting H. pylori toxicity. Aims: To evaluate gastric fibroblasts' expression of hepatocyte growth fact or (HGF), which is known to facilitate gastric ulcer healing, in the presen ce of H. pylori; to compare the effect on H. pylori-induced HGF expression of a COX-2 selective inhibitor with that of nonselective nonsteroidal anti- inflammatory drugs (NSAIDs). Methods: Human gastric fibroblasts were cultured from human gastric mucosa obtained at surgery. Prostaglandin E-2 (PGE(2)) and HGF were measured by EI A. The expression of COX-2 mRNA was assessed by the TaqMan quantitative RT- PCR system. Results: H. pylori increased PGE(2) release in gastric fibroblasts. H. pylo ri induced expression of COX-2 mRNA, which indicates that PG induction by H . pylori is through COX-2. Sulindac sulphide, etodolac and NS 398 all inhib ited H. pylori-induced PGE(2) release to the same extent. These agents also inhibited H. pylori-induced HGF release. Conclusion: Gastric fibroblasts produce PG and HGF in response to the prese nce of H. pylori, which may be considered part of the human body's defensiv e reaction to H. pylori toxicity. This defensive mechanism is inhibited not only by COX-2 nonselective NSAIDs but also by a COX-2 selective inhibitor. These findings indicate the importance of COX-2 in chronic H. pylori infec tion.