The effect of NSAIDs and a COX‐2 specific inhibitor on Helicobacter pylori‐induced PGE₂ and HGF in human gastric fibroblasts

Abstract

Summary Background: 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. Aims: 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. 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 E2 (PGE2) and HGF were measured by EIA. The expression of COX‐2 mRNA was assessed by the TaqMan quantitative RT‐PCR system. Results: H. pylori increased PGE2 release in gastric fibroblasts. H. pylori 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 inhibited H. pylori‐induced PGE2 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 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 COX‐2 nonselective NSAIDs but also by a COX‐2 selective inhibitor. These findings indicate the importance of COX‐2 in chronic H. pylori infection.

Aspirin Use and the Risk of Gastric Cancer: A Meta-Analysis

“…Until now, the anti-cancer mechanism of aspirin remains unclear. It is possible that aspirin may inhibit the replication and proliferation of H. pylori, and neutralize the increased COX-2 expression and prostaglandin synthesis associated with H. pylori infection, thereby reducing the risk of gastric cancer [43,44].…”

Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer

“…3) Gridley et al [47] and Thun et al [48] indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect patients against gastric cancer as well as colorectal cancer. Wang et al [49] reported that NSAID use has been associated with a reduced risk of gastric cancer and speculated that it is possible that NSAIDs may inhibit the replication and proliferation of H. pylori [49,50], while Takahashi et al [51] and Hudson et al [52] reported that NSAIDs may neutralize the increased cyclooxygenase-2 (COX-2) expression and prostaglandin synthesis associated with H. pylori infection, thereby reducing the risk of gastric cancer. However, these drugs may also cause peptic ulcers [53], so that long-term NSAID use may be associated with an increased risk of gastroduodenal ulcer and a reduced risk of gastric cancer, but there are some negative opinions about this association [54,55], and so there is no consensus regarding the anticancer effects of NSAIDs.…”

Involvement of cyclooxygenase‐2 in hyperplastic gastritis induced by Helicobacter pylori infection in C57BL/6 mice

“…Takahashi et al . reported that H. pylori increased the PGE 2 and HGF releases from human gastric fibroblasts and that these increased releases were inhibited by NSAIDs including a COX‐2 specific inhibitor 50 . Several studies showed that H. pylori infection can cause increased gastric cell proliferation, which is assumed to play an important role in gastric carcinogenesis 6 –8 .…”