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Investigation of Kampo medicine mechanism against the infection via type 1 interferon producing cells

Research Project

Project/Area Number 21390224
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionKeio University

Principal Investigator

WATANABE Kenji  慶應義塾大学, 医学部, 准教授 (70191757)

Co-Investigator(Renkei-kenkyūsha) NAGASAKI Masao  東京大学, 医科学研究所, 助教 (90396862)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Keywords十全大補湯 / インターフェロンα / toll like receptor / MyD88 / ノックアウトマ / ノックアウトマウス / toll like receptor 4
Research Abstract

We have found the Kampo medicine, juzentaihoto acts on interferon(IFN) gene expression signal pathway and controls the IFN production. For the further investigation of the mechanisms of IFN production, we have tried to identify the IFN producing cells in the large intestine and Kampo drugs action mechanisms. Analysis of toll like receptor 4(TLR-4) and MyD 88 knock-out mice, the mechanism of action of juzentaihoto was observed via TLR-4 dependent and MyD88 independent signal pathway. In the MyD88 knock-out mouse, type 1 IFN related genes, like IRF-7 was elevated. This elevation was also observed in the germ free mouse. Among all these mice, certain type of monocytes played an important role. These monocytes have not identified yet. In order to investigate the role of juzentaihoto on the influenza infection, we applied juzentaihoto to C57BL/6 mouse. However the protective action against influenza virus was stronger with hochuekkito than with juzentaihoto. We investigated the mechanism of action of hochuekkito against the influenza virus and found the defensin 4 was elevated in vivo. In vitro experiments, adhesion of influenza virus to MDCK cells was inhibited by hochuekkito. These mechanism may explain the effectiveness of hochuekkito against the influenza virus.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (19 results)

All 2012 2011 2010 2009 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (11 results) Remarks (1 results)

  • [Journal Article] Microarray analysis on germfree mice elucidates the primary target of a traditional Japanese medicine juzentaihoto : acceleration of IFN-αresponse via affecting the ISGF3-IRF7 signaling cascade2012

    • Author(s)
      Munakata K, Takashima K, Nishiyama M, Asano N, Mase A, Hioki K, Ohnishi Y, Yamamoto M, Watanabe K
    • Journal Title

      BMC Genomics

      Volume: 13 Pages: 30-30

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microarray analysis on germfree mice elucidates the primary target of a traditional Japanese medicine juzentaihoto : acceleration of IFN-α response via affecting the ISGF3-IRF7 signaling cascade2012

    • Author(s)
      Kaori Munakata, kiyoe Takashima, Mitsue Nishiyama, Naoko Asano, Akihito Mase, Kyoji Hioki, Yasuyuki Ohnishi, Masahiro Yamamoto, Kenji Watanabe
    • Journal Title

      BMC Genomics

      Volume: 13:30 Issue: 1

    • DOI

      10.1186/1471-2164-13-30

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 漢方薬十全大補湯が大腸のIFN-alpha産生に及ぼす影響2010

    • Author(s)
      宗形佳織、渡辺賢治
    • Journal Title

      消化と吸収

      Volume: Vol.32 No.2 Pages: 185-188

    • NAID

      10027054642

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大腸におけるインターフェロンαの産生に対する十全大補湯の作用: MyD88、TLR4ノックアウトマウスを用いた解析2010

    • Author(s)
      皆川紗代、宗形佳織、渡辺賢治
    • Journal Title

      消化と吸収

      Volume: Vol.32 No.2 Pages: 181-184

    • NAID

      10027054636

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 大腸におけるインターフェロンαの産生に対する十全大補湯の作用:MyD88、TLR4ノックアウトマウスを用いた解析2010

    • Author(s)
      皆川紗代、宗形佳織、渡辺賢治
    • Journal Title

      消化と吸収

      Volume: Vol.32 No.2 Pages: 181-184

    • NAID

      10027054636

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intestinal flora induces the expression of Cy3pa in the liver2009

    • Author(s)
      Toda T, Watanabe K, et.al.
    • Journal Title

      Xenobiotica 39(4)

      Pages: 323-334

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Orengedokuto and berberine improve ingdomethacin-induced small intestinal inhury via adenosine2009

    • Author(s)
      Watanabe Y, Watanabe K, et.al
    • Journal Title

      J.Gastroenterol 44(5)

      Pages: 380-389

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 補中益気湯の抗Influenza virus作用2011

    • Author(s)
      宗形佳織
    • Organizer
      第11回日本臨床中医薬学会学術大会
    • Place of Presentation
      東京・慶應義塾大学北里講堂
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] 十全大補湯により誘導される大腸のIFNα産生細胞の解析2010

    • Author(s)
      宗形佳織、榎本成志、山本雅浩、渡辺賢治
    • Organizer
      和漢医薬学会学術大会
    • Place of Presentation
      京都薬科大学
    • Year and Date
      2010-08-29
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Effect of Japanese herbal medicine(Kampo) on the survival of mice infected with influenza virus2010

    • Author(s)
      Munakata K, Yamamoto M, Watanabe K
    • Organizer
      ICCMR 2010
    • Place of Presentation
      Tromso, Norway
    • Year and Date
      2010-05-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of Japanese herbal medicine (Kampo) on the survival of mice infected with influenza virus.2010

    • Author(s)
      K Munakata, M Yamamoto
    • Organizer
      ICCMR 2010
    • Place of Presentation
      Tromso, Norway
    • Year and Date
      2010-05-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 免疫・アレルギー疾患の漢方治療2009

    • Author(s)
      渡辺賢治
    • Organizer
      第28回漢方免疫アレルギー研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-06-27
    • Related Report
      2011 Final Research Report
  • [Presentation] 免疫・アレルギー疾患の漢方治療2009

    • Author(s)
      渡辺賢治
    • Organizer
      第28回漢方免疫アレルギー研究会学術集
    • Place of Presentation
      東京
    • Year and Date
      2009-06-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 漢方薬十全大補湯が大腸のIFN alpha産生に及ぼす影響2009

    • Author(s)
      宗形佳織、渡辺賢治
    • Organizer
      第40回日本消化吸収学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 大腸におけるIFN alphaの産生調節機構の解明2009

    • Author(s)
      皆川紗代、宗形佳織、渡辺賢治
    • Organizer
      第40回日本消化吸収学会総会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 十全大補湯による大腸インターフェロンα産生促進の作用機序2009

    • Author(s)
      皆川紗代、宗形佳織、山本雅浩、渡辺賢治
    • Organizer
      第26回和漢医薬学会学術大会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 大腸におけるIFN alpha の産生調節機構の解明2009

    • Author(s)
      皆川紗代, 宗形佳織, 渡辺賢治
    • Organizer
      第40回日本消化吸収学会総会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] 漢方薬十全大補湯が大腸のIFN alpha 産生に及ぼす影響2009

    • Author(s)
      宗形佳織, 渡辺賢治
    • Organizer
      第40回日本消化吸収学会総会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Remarks] 慶應義塾大学医学部漢方医学センター

    • URL

      http://web.sc.itc.keio.ac.jp/kampo/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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