Role of intestinal macrophages in the pathogenesis of intestinal lesions induced by non-steroidal anti-inflammatory drugs.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: KATO Shinichi Kyoto Pharmaceutical University, 薬学部, 准教授 (90281500)
• Project Period (FY): 2008 – 2010
• Keywords: 非ステロイド性抗炎症薬(NSAID) / マクロファージ / 消化管傷害 / α7ニコチン性アセチルコリン受容体 / 内皮型NO合成酵素 / 一酸化窒素(NO)

Research Abstract

In the present study, we investigated the role intestinal macrophages in the pathogenesis of gastrointestinal diseases.
1. The activation of α7 nicotinic acetylcholine receptor (α7nAChR) suppresses the severity of intestinal lesions induced by non-steroidal anti-inflammatory drugs (NSAID).
2. Dopamine D2 receptor antagonists significantly prevent NSAID-induced intestinal lesions through activation ofα7nAChR.
3. The aggravation of NSAID-induced gastric damage during arthritis is attributable to the upregulation of iNOS and eNOS.
4. Lansoprazole, a proton pump inhibitor, protects NSAID-induced intestinal lesions through induction of heme oxygenase (HO)-1.
5. Macrophages play a beneficial role in the healing of chronic gastric ulcers mediated by increase in neovascularization through upregulation of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF).

Research Products

• [Journal Article] Activation of α7 nicotinic acetylcholine receptors ameliorates indomethacin-induced small intestinal ulceration in mice (2011)
  • Author(s): Kawahara R, Yasuda M, Hashimura H, Amagase K, Kato S, Takeuchi K
  • Journal Title: European Journal of Pharmacology 650 Pages: 248-261
  • Peer Reviewed
• [Journal Article] Roles of COX inhibition in pathogenesis of NSAID-induced small intestinal damage (2010)
  • Author(s): Takeuchi K, Tanaka A, Kato S, Amagase K, Satoh H
  • Journal Title: Clinica Chimica Acta 411 Pages: 459-466
  • Peer Reviewed
• [Journal Article] Prevention by lansoprazole, a proton pump inhibitor, of indomethacin-induced small intestinal ulceration in rats. (2010)
  • Author(s): Yoda Y, Amagase K, Kato S, Tokioka S, Murano M, Kakimoto K, Nishio H, Umegaki E, Takeuchi K, Higuchi K.
  • Journal Title: Journal of Physiology and Pharmacology 61 Pages: 287-294
  • Peer Reviewed
• [Journal Article] Role of endothelial nitric oxide synthase in aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats. (2009)
  • Author(s): Kato S, Ohkawa F, Ito Y, Takeuchi K.
  • Journal Title: Journal of Physiology and Pharmacology 60 Pages: 147-155
  • Peer Reviewed
• [Journal Article] Aggravation of cold-restraint stress-induced gastric lesions in adjuvant arthritic rats : pathogenic role of inducible and endothelial nitric oxide. (2009)
  • Author(s): Kato S, Kawahara R, Yasuda M, Amagase K, Takeuchi K.
  • Journal Title: Journal of Pharmacological Sciences 111 Pages: 244-252
  • Peer Reviewed
• [Presentation] α7ニコチン受容体活性化によるインドメタシン誘起小腸傷害の抑制 (2011)
  • Author(s): 河原良治、安田仁、橋村寛、天ヶ瀬紀久子、加藤伸一、竹内孝治
  • Organizer: 第7回日本消化管学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2011-02-18
• [Presentation] Different mechanisms of effective PPIs or H2-blockers for prevention of NSAID-induced small intestinal damage. (2010)
  • Author(s): Yoda Y, Amagase K, Kato S, Tokioka S, Murano M, Kakimoto K, Takeuchi K, Higuchi K.
  • Organizer: 米国消化器病学会
  • Place of Presentation: 米国ニューオリンズ
  • Year and Date: 2010-05-03
• [Presentation] α7ニコチン受容体活性化によるインドメタシン誘起小腸傷害の抑制効果 (2010)
  • Author(s): 河原良治、安田仁、天ヶ瀬紀久子、加藤伸一、竹内孝治
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-18