title: The effect of NSAIDs and a COX-2 specific inhibitor on Helicobacter pylori-induced PGE2 and HGF in human gastric fibroblasts.
abstract: 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.
  
  
  OBJECTIVE
  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
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital at Koshigaya, Dokkyo University School of Medicine, Saitama, Japan. mtak@dokkyomed.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: H
authors.initials: H
authors.lastname: Takada
authors.forename: H
authors.initials: H
authors.lastname: Kuwayama
authors.forename: A
authors.initials: A
authors.lastname: Terano
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology*; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000503:physiopathology*; D016480:Helicobacter pylori; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D013276:Stomach Ulcer / Q000382:microbiology* / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D017228:Hepatocyte Growth Factor; D015232:Dinoprostone