The effect of NSAIDs and COX-2 specific inhibitor on Helicobacter pylori-induced PGE[sub2] and HGF in human gastric fibroblasts.

There is compelling evidence for the pivotal role of Helicobacter pylori in the pathogenesis of gastrointestinal ulcer disease. However, despite the bacterium’s toxicity, the majority of H. pylori infections are not accompanied by gastric ulcers. This implies the existence of a host mechanism offsetting H. pylori toxicity. To evaluate gastric fibroblasts’ expression of hepatocyte growth factor (HGF), which is known to facilitate gastric ulcer healing, in the presence of H. pylori; to compare the effect on H. pylori­induced HGF expression of a COX­2 selective inhibitor with that of nonselective nonsteroidal anti­inflammatory drugs (NSAIDs).Human gastric fibroblasts were cultured from human gastric mucosa obtained at surgery. Prostaglandin E[sub2] (PGE[sub2]) and HGF were measured by EIA. The expression of COX­2 mRNA was assessed by the TaqMan quantitative RT­PCR system. H. pylori increased PGE[sub2] release in gastric fibroblasts. H. pylori induced expression of COX­2 mRNA, which indicates that PG induction by H. pylori is through COX­2. Sulindac sulphide, etodolac and NS 398 all inhibited H. pylori­induced PGE[sub2] release to the same extent. These agents also inhibited H. pylori­ induced HGF release. Gastric flbroblasts produce PG and HGF in response to the presence of H. pylori, which may be considered part of the human body’s defensive reaction to H. pylori toxicity. This defensive mechanism is inhibited not only by COX­2 nonselective NSAIDs but also by a COX­2 selective inhibitor. These findings indicate the importance of COX­2 in chronic H. pylori infection. [ABSTRACT FROM AUTHOR]