Role of cyclooxygenase-2 in Helicobacter pylori- induced gastritis in Mongolian gerbils.
Cyclooxygenase (COX)-2 expression is induced in the gastric mucosa of Helicobacter pylori-infected patients, but its role remains unclear. We examined the effects of NS-398 and indomethacin on gastric pathology in H. pylori-infected Mongolian gerbils. COX-1 was detected in both normal and H. pylori-infected mucosa, whereas COX-2 was expressed only in the infected mucosa. PGE(2) production was elevated by H. pylori infection, and the increased production was reduced by NS-398, which did not affect PGE(2) production in normal mucosa. Indomethacin inhibited PGE(2) production in both normal and infected mucosa. Hemorrhagic erosions, neutrophil infiltration, lymphoid follicles, and epithelium damage were induced by H. pylori infection. NS-398 and indomethacin aggravated these pathological changes but did not increase viable H. pylori number. H. pylori-increased production of neutrophil chemokine and interferon-gamma was potentiated by NS-398 and indomethacin. Neither NS-398 nor indomethacin caused any pathological changes or cytokine production in normal animals. These results indicate that COX-2 as well as COX-1 might play anti-inflammatory roles in H. pylori-induced gastritis.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan. takahasi@mb.kyoto-phu.ac.jp
Fujita
T
T
Yamamoto
A
A
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis*; D002630:Chemotactic Factors / Q000096:biosynthesis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000473:pathology; D005849:Gerbillinae; D006131:Growth Inhibitors / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis; D016481:Helicobacter Infections / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D018925:Chemokines; D002630:Chemotactic Factors; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006131:Growth Inhibitors; D006133:Growth Substances; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D007371:Interferon-gamma; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin