title: Anti-inflammatory effect of two isoforms of COX in H. pylori-induced gastritis in mice: possible involvement of PGE2.
abstract: Neutrophil infiltration mediated by TNF-alpha is associated with various types of gastric injury, whereas PGs play a crucial role in gastric defense. We examined roles of two isoforms of cyclooxygenase (COX) and PGE2 in Helicobacter pylori-induced gastritis in mice. Mice infected with H. pylori were given selective COX-1 inhibitor SC-560 (10 mg/kg), selective COX-2 inhibitor NS-398 (10 mg/kg), or nonselective COX inhibitor indomethacin (2 mg/kg) with or without 16,16-dimethyl PGE2 for 1 wk. H. pylori infection increased levels of mRNA for COX-1 and -2 in gastric tissue by 1.2-fold and 3.3-fold, respectively, accompanied by a significant increase in PGE2 production by gastric tissue. H. pylori infection significantly elevated MPO activity, a marker of neutrophil infiltration, and epithelial cell apoptosis in the stomach. SC-560 augmented MPO activity and epithelial cell apoptosis with associated reduction in PGE2 production, whereas NS-398 had the same effects without affecting PGE2 production. Inhibition of both COX-1 and -2 by indomethacin or concurrent treatment with SC-560 and NS-398 resulted in a stronger increase in MPO activity and apoptosis than inhibition of either COX-1 or -2 alone. H. pylori infection elevated TNF-alpha mRNA expression in the stomach, which was further increased by indomethacin. Effects of COX inhibitors on neutrophil infiltration, apoptosis, and TNF-alpha expression in H. pylori-infected mice were abolished by exogenous 16,16-dimethyl PGE2. In conclusion, PGE2 derived from either COX-1 or -2 is involved in regulation of gastric mucosal inflammation and contributes to maintenance of mucosal integrity during H. pylori infection via inhibition of TNF-alpha expression.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masaki
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Sasaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Oshitani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology; D005756:Gastritis / Q000201:enzymology* / Q000473:pathology; D016481:Helicobacter Infections / Q000201:enzymology* / Q000473:pathology; D016480:Helicobacter pylori; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D007213:Indomethacin