title: Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice.
abstract: BACKGROUND
  Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice.
  
  
  METHODS
  Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined.
  
  
  RESULTS
  Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment.
  
  
  CONCLUSIONS
  Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Miyake
authors.forename: Taku
authors.initials: T
authors.lastname: Tsukui
authors.forename: Ken
authors.initials: K
authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tatsuguchi
authors.forename: Seiji
authors.initials: S
authors.lastname: Futagami
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: Kei
authors.initials: K
authors.lastname: Shinoki
authors.forename: Tadasu
authors.initials: T
authors.lastname: Iizumi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Akamatsu
authors.forename: Choitsu
authors.initials: C
authors.lastname: Sakamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D007150:Immunohistochemistry / Q000379:methods; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D023421:Models, Animal; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007509:Irritants; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000431:Ethanol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D007213:Indomethacin