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Pathophysiological Role of Cholinergic Anti-inflammatory Pathway via Nicotinic Acetylcholine Receptors in Experimental Ulcerative Colitis

Research Project

Project/Area Number 18590507
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionUniversity of Toyama

Principal Investigator

KADOWAKI Makoto  University of Toyama, Institute of Natural Medicine, Professor (20305709)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Takeshi  University of Toyama, Institute of Natural Medicine, Assistant Professor (70316181)
KURAMOTO Hirofumi  University of Toyama, Deapartment of Applied Biology, Associate Professor (30153373)
SUGIYAMA Toshito  University of Toyama, School of Medicine, Professor (00196768)
KADOWAKI Takashi  The University of Tokyo, School of Medicine, Professor (30185889)
KAGEYAMA Natsuko  University of Toyama, Institute of Natural Medicine, Assistant Professor (90342865)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsulcerative Colitis / oxazolone / nicotinic acetylcholine receptor s / intestinal mucosal immune system / type-2 helper T cell / cytokine / ニコチン受容体
Research Abstract

It has been reported that the cholinergic anti-inflammatory pathway that is controlled by the vagus nerve inhibits local cytokine release. Epidemiologic reports suggest that smoking and nicotine may improve the symptoms of ulcerative colitis(UC. The purpose of the present study was to investigate the pathophysiological role of vagus nerve in oxazolone (OXZ)-induced Th2 type UC model. METHODS: OXZ was injected into the colon of BALB/c mice (Th2 dominant strain). OXZ colitis was assessed in the colon with the disease activity score(DAS), pathological colonic damage score(CDS) by macroscopic evaluation and MPO. RESULT: OXZ-treated mice developed colitis marked by increase of DAS, CDS and MPO in the colon of the OXZ colitis. The central stimulation of vagus nerves by 2-deoxy-d-glucose significantly improved DAS, CDS and MPO and nicotine significantly alleviated the OXZ colitis in a dose-dependent fashion. Notably, hexamethonium and α7-nicotinic acetylcholine receptor (nAChR) antagonist methyllycaconitine significantly prevented the therapeutic effects of nicotine in OXZ colitis. Transcript levels of Th2 cytokines (IL-4, IL-5, and IL-10) significantly increased in the spleen and the colon of OXZ colitis mice. On the other hand, Thl cytokine, IFN-γ mRNA significantly decreased in the spleen and significantly increased in the middle colon. Noteably, both Thl and Th2 cytokines mRNAs were significantly down-regulated in the spleen and colon of nicotine-treated mice. Moreover, to identify α7-nAChR in the colon, unfixed cryosections of colon from OXZ colitis mice were stained with FITC-labelled α-bungarotoxin (α-BTx; α7-nAChR antagonist). Α-BTx-binding cells were upregulated in the OXZ colitis colon, and nicotine pretreatment abolished the fluorescence of α-BTx. CONCLUSION: The vagal anti-inflammatory and immune pathway acts through α7-nAChR in the mucosa of the colon to alleviate inflammation in the colon.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (36 results)

All 2008 2007 2006 Other

All Journal Article (17 results) (of which Peer Reviewed: 9 results) Presentation (19 results)

  • [Journal Article] The pathophysiological roles of COX-1 and COX-2 in the intestinal smooth muscle contractility under the anaphylactic condition.2008

    • Author(s)
      Kadowaki H
    • Journal Title

      Biomedical Research 29

      Pages: 113-117

    • NAID

      130004724049

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The pathophysiological roles of COX-1 and COX-2 in the intestinal smooth muscle contractility under the anaphylactic condition2008

    • Author(s)
      Kadowaki H
    • Journal Title

      Biomedical Research (掲載確定)

    • NAID

      130004724049

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation in aquaporin 4 and aquaporin 8 expression of the colon associated with the induction of allergic diarrhea in a mouse model of food allergy.2007

    • Author(s)
      Yamamoto T
    • Journal Title

      Life Sciences 81

      Pages: 115-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Distinct morphology of serotonin-containing enterochromaffin(EC)cells in the rat distal colon.2007

    • Author(s)
      Kuramoto H
    • Journal Title

      Archives of Histology and Cytology 70

      Pages: 235-241

    • NAID

      10021186774

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Downregulation in aquaporin 4 and aquaporin 8 expression of the colon associated with the induction of allergic diarrhea in a mouse model of food allergy2007

    • Author(s)
      Yamamoto, T
    • Journal Title

      Life Sciences 81

      Pages: 115-120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Distinct morphology of serotonin-containing enterochromaffin(EC)cells in the rat distal colon2007

    • Author(s)
      Kuramoto, H
    • Journal Title

      Archives of Histology and Cytology 70

      Pages: 235-241

    • NAID

      10021186774

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Downregulation in aquaporin 4 and aquaporin 8 expression of the colonassociated with the induction of allergic diarrhea in a mouse model of food allergy2007

    • Author(s)
      Yamamoto T
    • Journal Title

      Life Sciences 81

      Pages: 115-120

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Distinct morphology of serotonin-containing enterochromaffin (EC) cells in the rat distal colon2007

    • Author(s)
      Kuramoto H.
    • Journal Title

      Archives of Histology and Cytology 70

      Pages: 235-241

    • NAID

      10021186774

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calbindin is predominantly expressed in nitrergic neurons in rat esophagus.2006

    • Author(s)
      Kuramoto H
    • Journal Title

      Neuroscience Letters 401

      Pages: 174-177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Vagus nerve stimulation preferentially induces Fos expression in nitrergicneurons of rat esophagus.2006

    • Author(s)
      Kuramoto H
    • Journal Title

      Cell & Tissue Research 324

      Pages: 361-367

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Calbindin is predominantly expressed in nitrergic neurons in rat esophagus2006

    • Author(s)
      Kuramoto, H
    • Journal Title

      Neuroscience Letters 401

      Pages: 174-177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Vagus nerve stimulation preferentially induces Fos expression in nitrergic neurons of rat esophagus2006

    • Author(s)
      Kuramoto, H
    • Journal Title

      Cell & Tissue Research 324

      Pages: 361-367

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The pathophysiological roles of COX-1 and COX-2 in the intestinal smooth muscle contractility under the anaphylactic condition2006

    • Author(s)
      Kadowaki, H
    • Journal Title

      Biomedical Research 29

      Pages: 113-117

    • NAID

      130004724049

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Calbindin is predominantly expressed in nitrergic neurons in rat esophagus.2006

    • Author(s)
      Kuramoto H
    • Journal Title

      Neuroscience Letters 401・1-2

      Pages: 174-177

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Vagus nerve stimulation preferentially induces Fos expression in nitrergic neurons of rat esophagus.2006

    • Author(s)
      Kuramoto H
    • Journal Title

      Cell & Tissue Research 324・3

      Pages: 361-367

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Therapeutic effect of kakkonto on food allergy model mice with gastrointestinal symptoms

    • Author(s)
      Yamamoto T
    • Journal Title

      International Archives of Allergy and Immunology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Therapeutic effect of kakkonto on food allergy model mice with gastrointestinal symptoms

    • Author(s)
      Yamamoto, T
    • Journal Title

      International Archives of Allergy and Immunology(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cholinergic anti-inflammatory pathway through α7-nicotinic acetylcholine receptors in the colon reduces oxazolone-induced colitis in mouse.2007

    • Author(s)
      Kadowaki M.
    • Organizer
      Falk Workshop"Mechanisms of Intestinal Inflammation"
    • Place of Presentation
      Dresden, Germany.
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cholinergic anti-inflammatory pathway through α7-nicotinic acetylcholine receptors in the colon reduces oxazolone-induced colitis in mouse2007

    • Author(s)
      Kadowaki, M
    • Organizer
      Falk Workshop "Mechanisms of Intestinal Inflammation"
    • Place of Presentation
      Dresden, Germany
    • Year and Date
      2007-10-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chohnergic anti-inflammatory pathway through α7-nicotinic acetylcholinle receptors in the colon reduces oxazolone-induced colitis in mouse2007

    • Author(s)
      Kadowaki M.
    • Organizer
      Falk workshop "Mechaisms of Intestinal lnflammation"
    • Place of Presentation
      Dresden, Germany
    • Year and Date
      2007-10-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pathophysiological Role of Vagal Anti-inflammatory Pathway via α7-Nicotinic Receptors in Experimental Ulcerative Colitis.2007

    • Author(s)
      Kadowaki M.
    • Organizer
      5th Congress of the International Society for Autonomic Neuroscience.
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathophysiological Role of Vagal Anti-inflammatory Pathway via α7-Nicotinic Receptors in Experimental Ulcerative Colitis2007

    • Author(s)
      Kadowaki, M
    • Organizer
      5th Congress of the International Society for Autonomic Neuroscience
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Stimulation of Vagus Nerve Attenuates Inflammation by Activating alpha7 Nicotinic Acetylcholine Receptors in the Colon of Oxazolone-Induced Ulcerative Colitis Mouse2007

    • Author(s)
      Yamamoto T.
    • Organizer
      International Congress of Mucosal Immunology.
    • Place of Presentation
      京都
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pathophysiological Role of Vagal Anti-inflammatory Pathway via α7-Nicotinic Receptors in Experimental Ulcerative Colitis.2007

    • Author(s)
      Kadowaki M.
    • Organizer
      5th Congress of the International Society for Autonomic Neuroscience.
    • Place of Presentation
      京都
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] Stimulation of Vagus Nerve Attenuates Inflammation by Activating alpha7 Nicotinic Acetylcholine Receptors in the Colon of Oxazolone-Induced Ulcerative Colitis Mouse.2007

    • Author(s)
      Yamamoto T.
    • Organizer
      International Congress of Mucosal Immunology.
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-07-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Stimulation of Vagus Nerve Attenuates Inflammation by Activating alpha7 Nicotinic Acetylcholine Receptors in the Colon of Oxazolone-Induced Ulcerative Colitis Mouse2007

    • Author(s)
      Yamamoto, T
    • Organizer
      International Congress of Mucosal Immunology
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-07-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Stimulation of Vagus Nerve Attenuates Inflammation by Activating α7 Nicotinic Acetylcholine Receptors on CD4+T Cells in the Colon of Oxazolone-Induced Ulcerative Colitis Mouse.2007

    • Author(s)
      Yoshida M
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington DC, U. S. A.
    • Year and Date
      2007-05-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Therapeutic Effects of Saireito, a Traditional Herbal Medicine, in Oxazolone-Induced Mouse Ulcerative Colitis via the Suppression of Enhanced Expression of the Suppressor of Cytokine Signaling(SOCS)-3.2007

    • Author(s)
      Watanabe T.
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington DC, U. S. A.
    • Year and Date
      2007-05-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Stimulation of Vagus Nerve Attenuates Inflammation by Activating α7 Nicotinic Acetylcholine Receptors on CD4+ T Cells in the Colon of Oxazolone-Induced Ulcerative Colitis Mouse2007

    • Author(s)
      Yoshida, M
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington DC., U. S. A.
    • Year and Date
      2007-05-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Therapeutic Effects of Saireito, a Traditional Herbal Medicine, in Oxazolone-Induced Mouse Ulcerative Colitis via the Suppression of Enhanced Expression of the Suppressor of Cytokine Signaling(SOCS)-32007

    • Author(s)
      Watanabe, T
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington DC., U. S. A.
    • Year and Date
      2007-05-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Stimulation of vagus Nerve Attenuates Inflammation by Activating α7 Nicotinic Acetylchoholie Receptors on CD4+T Cells in the Colo of Oxazolone-lnduced Ulcerative Colitis Mouse.2007

    • Author(s)
      Yoshida M
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington D.C., U.S.A.
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Therapeutic Effects of Saireito, a Traditinal Herbal Medicine, in Oxazolone-Induced Mouse Ulcerative Colitis via the Suppression of EnhancedExpreesion of the Suppressor of Cytokine Signaing (SOCS)-32007

    • Author(s)
      Watanabe T.
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Washington D.C., U.S.A
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] THERAPEUTIC EFFECT OF KAMPO MEDICINE, SAIREITO IN A MURINE MODEL OF THELPER CELL TYPE 2 COLITIS.2006

    • Author(s)
      Yoshida M
    • Organizer
      The 7th Joint Seminar"Recent Advances in Natural Product Research and its Application"
    • Place of Presentation
      富山
    • Year and Date
      2006-12-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] THERAPEUTIC EFFECT OF KAMPO MEDICINE, SAIREITO IN A MURINE MODEL OF THELPER CELL TYPE 2 COLITIS2006

    • Author(s)
      Yoshida, M
    • Organizer
      The 7th Joint Seminar "Recent Advances in Natural Product Research and its Application"
    • Place of Presentation
      Toyama
    • Year and Date
      2006-12-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] PATHOPHYSIOLOGICAL ROLE OF THE CHOLINERGIC ANTI-INFLAMMATORY AND IMMUNE PATHWAY IN MOUSE OXAZOLONE-INDUCED ULCERATIVE COLITIS MODEL.2006

    • Author(s)
      Yamamoto T
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Los Angeles, U. S. A.
    • Year and Date
      2006-05-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] PATHOPHYSIOLOGICAL ROLE OF THE CHOLINERGIC ANTI-INFLAMMATORY AND IMMUNE PATHWAY IN MOUSE OXAZOLONE-INDUCED ULCERATIVE COLITIS MODEL2006

    • Author(s)
      Yamamoto, T
    • Organizer
      Digestive Disease Week
    • Place of Presentation
      Los Angeles, U. S. A.
    • Year and Date
      2006-05-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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