analysis of cytoprotection by COX-2 induced in gastric mucosa : influence by selective COX-2 inhibitors

• Project/Area Number: 12670526
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nippon Medical School
• Principal Investigator: MIYAKE Kazumasa Nippon Medical School, Third department of Internal Medicine, Assistant, 医学部, 助手 (60247012)
• Co-Investigator(Kenkyū-buntansha): SAKAMOTO Choitsu Nippon Medical School, Third department of Internal Medicine, Assistant, 医学部, 教授 (30196092)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: cyclooxygenase-2 / selective COX-2 inhibitors / gastric mucosal injury / ethanol / NS 398 / Indomethacin / Cyclooxygenase / VEGF / 粘膜保護作用 / 選択的COX2阻害剤 / 胃

Research Abstract

Purpose : Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reduce gastric injury caused by irritants given subsequently. The aim of the study is to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment is involved in prevention of subsequent ethanol-caused gastric injury in mice. Methods : Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression was immunohistochemically determined at every 8 hours in the stomachs. Mice were administered 95 % ethanol 24 hours after acidified ethanol pretreatment and gastric mucosal damages were evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on 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 its peak level 24 hours after the pretreatment. 95 % ethanol caused gastric mucosal damages. The degree of the damages was not different between mice pretreated with acidified ethanol and saline. However, NS-398 aggravated ethanol-caused damages only in mice pretreated with acidified ethanol, while indomethacin aggravated the damages evaluated histologically Irrespective of the pretreatment. Conclusions : The pretreatment- induced COX-2 in addition to COX-1 seems to be involved in the defense mechanism through minimizing damages caused by a subsequent irritant.

Research Products

• [Publications] Miyake K, Tsukui: "Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice"J Gastroenterol. 37.3(in press). (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Miyake K, Tsukui T et al.: "Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection"Aliment Pharmacol Ther. 16(S2). 1-7 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Futagami S, Miyake K et al.: "Inhibition of helicobacter pylori-induced cox-2 agravates NSAID-caused gastric damage in Mongolian gerbils"Aliment Pharmacol Ther. (in press). (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tsukui T, Miyake K et al.: "Aging increases and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia"J of Gastroenterology and Hepatology. 16. 15-21 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tatsuguchi A, Miyake K et al.: "Localization of cyclooxygenase-1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissue in humans"GUT. 46(16). 782-789 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tatsuguchi A, Miyake K et al.: "Induction of cyclooxygenase-2 in mesothelial cells in peritonitis caused by perforated ulcers -an immunohistochemical study in humans"Aliment Pharmacol Ther. 14(Suppl.1). 58-63 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 三宅一昌, 坂本長逸: "症例から学ぶ胃の病理 9.消化性潰瘍総論と特殊胃潰瘍"Modern physician. 1461-5 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Miyake K, Tsukui T, Wada K, Tatsuguchi A, Futagami S, Hiratsuka T, Shinoki K, Iizumi T, Akamatsu T, Sakamoto C, Kobayashi M.: "Irritant-induced cyclooxygenase-2 is involved in the defence mechanism of the gastric mucosa in mice"J Gastroenterol. 37(3) (in press). (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyake K, Tsukui T, Futagami S, Tatsuguchi A, Shinoki K, Hiratsuka T, Iizumi T, Nagata K, Shinji Y, Wada K, Yamada N, Kobayashi M, Sakamoto C.: "Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection"Aliment Pharmacol Ther. 16 (Suppl.2). 1-7 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Futagami S, Hiratsuka T, Wada K, Tatsuguchi A, Tsukui T, Miyake K, Akamatsu T, Hosone M, Sakamoto C.: "Inhibition of helicobacter pylori-induced COX-2 agravates NSAID-caused gastric damage in Mongolian gerbils"Aliment Pharmacol Ther. (in press). (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tsukui T, Kashiwagi R, Sakane M, Tabata F, Akamatsu T, Wada K, Futagami S, Miyake K, Sueoka N, Hirakawa T, Kobayashi M, Fujimori T, Sakamoto C.: "Aging increases and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia"Journal of Gastroenterology and Hepatolopy. 16. 15-21 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tatsuguchi A, Sakamoto C, Wada K, Akamatsu T, Tsukui T, Miyake K, Futagami S, Kishida T, Fukuda Y, Yamanaka N, Kobayashi M.: "Localization of cyclooxygenase-1 and cyclooxygenase-2 in Helicobacter pylori-related gastritis and gastric ulcer tissues in humans"Gut. 46(6). 782-789 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tatsuguchi A, Sakamoto C, Fukuda Y, Wada K, Akamatsu T, Tsukui T, Miyake K, Futagami S, Kishida T, Yamanaka N, Kobayashi M.: "Induction of cyclooxygenase-2 in mesothelial cells in peritonitis caused by perforated ulcers - an immunohistochemical study in humans"Aliment Pharmacol Ther. 14 (Suppl. 1). 58-63 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyake K., Tsukui T. et al.: "Irritant-induced cyclooxygenase-2 is incolved in the defeuse mechanism of the gastric mucosa in mice"J Gastroentcrol. 37・3(In press). (2002)
• [Publications] Miyake K., Tsukui T. et al.: "Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection"Aliment Pharmacol Ther. (In press). (2002)
• [Publications] Futagami S., Miyake K. et al.: "Inhibition of helicobacter pylori-induced COX-2 agravates NSAID-caused gastric damage in Mongolian gerbils"Aliment Pharmacol Ther. (In press). (2002)
• [Publications] Tsukui T., Miyake K. et al.: "Aging increases and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanese patients with dyspepsia"Journal of Gastroenterology and Hepatology. 16. 15-21 (2001)
• [Publications] Tatsuguchi A., Miyake K. et al.: "Localisation of cyclooxygenase-1 and cyclooxygenase-2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans"Gut. 46(6). 782-789 (2000)
• [Publications] Tatsuguchi A., Miyake K. et al.: "Induction of cyclooxygenase-2 in mesothelial cells in peritonitis caused by perforated ulcers-an immunohistochemical study in humans"Aliment Pharmacol Ther. 14(Suppl 1). 58-63 (2000)
• [Publications] 三宅一昌, 坂本長逸: "症例から学ぶ胃の病理 9.消化性潰瘍総論と特殊胃潰瘍"Modem physician. 1461-1465 (2001)
• [Publications] Tatsuguchi A: "Localisation of cyclooxygenase 1 and cycloxygenase 2 in Helicobacter pylori related gastritis and gastric alcer tissue in human"GUT. 46(6). 782-789 (2000)