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: Tetsuya Tanigawa, Toshio Watanabe, Masaki Hamaguchi, Eiji Sasaki, Kazunari Tominaga, Yasuhiro Fujiwara, Nobuhide Oshitani, Takayuki Matsumoto, Kazuhide Higuchi, Tetsuo Arakawa
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 286 Issue 1 Pg. G148-56 (Jan 2004) ISSN: 0193-1857 [Print] United States
• PMID: 12958020 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Membrane Proteins
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Thromboxane B2
• Cyclooxygenase 1
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Ptgs1 protein, mouse
• Dinoprostone
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cyclooxygenase 1
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (biosynthesis, pharmacology, physiology)
• Epithelial Cells (drug effects)
• Female
• Gastric Mucosa (enzymology, pathology)
• Gastritis (enzymology, pathology)
• Helicobacter Infections (enzymology, pathology)
• Helicobacter pylori
• Indomethacin (pharmacology)
• Isoenzymes (biosynthesis, physiology)
• Membrane Proteins
• Mice
• Mice, Inbred C57BL
• Prostaglandin-Endoperoxide Synthases (biosynthesis, physiology)
• RNA, Messenger (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Thromboxane B2 (biosynthesis)
• Tumor Necrosis Factor-alpha (biosynthesis)