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Regulation of intestinal and hepatic immunity and metabolism by vitamin D receptor

Research Project

Project/Area Number 25460394
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNihon University

Principal Investigator

MAKISHIMA Makoto  日本大学, 医学部, 教授 (70346146)

Co-Investigator(Renkei-kenkyūsha) SEKI Shuji  防衛医科大学校, 医学教育部医学科進学課程, 教授 (80531392)
UMEDA Kaori  日本大学, 医学部, 助手 (10445744)
ISHIZAWA Michiyasu  日本大学, 医学部, 助手 (30646542)
Research Collaborator YAMADA Sachiko  
NISHIDA Shigeru  
UMEDA Naoki  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsビタミンD受容体 / 肝障害 / クッパ-細胞 / NKT細胞 / 肝臓 / 胆汁酸 / サイトカイン / ビタミンD誘導体 / マクロファージ / 急性肝障害 / NK細胞 / クッパ-細胞 / 自然免疫 / インターロイキン6
Outline of Final Research Achievements

We examined the roles of vitamin D receptor (VDR) in immunity and metabolism in the liver and intestine. We compared the effects of inflammatory stimulants, such as lipopolysaccharide and concanavalin A, on hepatic immune cells isolated from wild-type mice and VDR knockout mice and their in vivo effects. VDR deletion reduced the inflammatory response of Kupffer cells and NK cells against lipopolysaccharide and alleviated concanavalin A-induced hepatitis. Experiments using a chenodeoxycholic acid-containing diet showed that metabolism of chenodeoxycholic acid and lithocholic acid is disturbed in VDR knockout mice. The results show that VDR plays a role in the hepatic immunity and bile acid metabolism. We developed selective VDR modulators, which should be useful for future studies.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] サンティアゴ・デ・コンポステーラ大学(スペイン)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Synthesis, Biological Activities and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds2015

    • Author(s)
      Yusuke Watarai, Michiyasu Ishizawa, Teikichi Ikura, Flavia C. M. Zacconi, Shigeyuki Uno, Nobutoshi Ito, Antonio Mourino, Hiroaki Tokiwa, Makoto Makishima, and Sachiko Yamada
    • Journal Title

      J.Med.Chem.

      Volume: 58 (24) Issue: 24 Pages: 9510-9521

    • DOI

      10.1021/acs.jmedchem.5b00792

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Therapeutic application of vitamin D receptor ligands: an updated patent review2015

    • Author(s)
      Ichiro Takada, and Makoto Makishima
    • Journal Title

      Expert Opinion on Therapeutic Patents

      Volume: 25 Issue: 12 Pages: 1373-1383

    • DOI

      10.1517/13543776.2015.1093113

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor2014

    • Author(s)
      Takeru Kudo, Michiyasu, Ishizawa, Kazuki Maekawa, Makoto Nakabayashi, Yusuke Watarai, Hikaru Uchida, Hiroaki Tokiwa, Teikichi Ikura, Nobutoshi Ito, Makoto Makishima, Sachiko Yamada,
    • Journal Title

      J. Med. Chem.

      Volume: 57(10) Issue: 10 Pages: 4073-4087

    • DOI

      10.1021/jm401989c

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 共役三重結合とアダマンチル基を導入したビタミンD誘導体の生物活性及びユニークな受容体結合様式2015

    • Author(s)
      石澤通康、渡會友祐、伊倉貞吉、Flavia C. M. Zacconi、Antonio Mourino、常盤広明、伊藤暢聡、山田幸子、槇島誠
    • Organizer
      第1回Neo Vitamin D Workshop学術集会
    • Place of Presentation
      大津プリンスホテル(滋賀県大津市)
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] ビタミンDと消化管2015

    • Author(s)
      槇島誠、石澤通康、西田滋
    • Organizer
      第1回Neo Vitamin D Workshop学術集会
    • Place of Presentation
      大津プリンスホテル(滋賀県大津市)
    • Year and Date
      2015-08-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 細胞選択的及び遺伝子選択的活性を有するビタミンD誘導体の生物活性評価2014

    • Author(s)
      石澤通康、高野真史、橘髙敦史、坂根里枝、須原義智、山田幸子、槇島誠
    • Organizer
      第344回脂溶性ビタミン総合研究委員会
    • Place of Presentation
      東京農業大学(東京都世田谷区)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 共役diyneとアダマンチル基を側鎖に有する19-ノルビタミンD誘導体の立体選択的合成と生物活性評価2013

    • Author(s)
      渡會友祐、前川和樹、石澤通康、宇野茂之、Antonio Mourino、槇島誠、常盤広明、山田幸子
    • Organizer
      第31回メディシナルケミストリーシンポジウム
    • Place of Presentation
      アステールプラザ(広島県)
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規VDRパーシャルアゴニストの立体選択的合成、X線結晶構造解析、および生物活性2013

    • Author(s)
      前川和樹、工藤健、渡會友祐、石澤通康、内田光、中林誠、伊藤暢聡、常盤広明、槇島誠、山田幸子
    • Organizer
      第31回メディシナルケミストリーシンポジウム
    • Place of Presentation
      アステールプラザ(広島県)
    • Related Report
      2013 Research-status Report
  • [Presentation] VDRパーシャルアゴニスト活性を示す新規ビタミンD誘導体の合成・生物活性

    • Author(s)
      渡會友祐、前川和樹、石澤通康、内田光、Flavia Zacconi、宇野茂之、常盤広明、Antonio Mourino、槇島誠、山田幸子
    • Organizer
      日本レチノイド研究会第24回学術集会
    • Place of Presentation
      星薬科大学百年記念館(東京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] ビタミンD受容体欠損マウスにおける胆汁酸代謝

    • Author(s)
      西田滋、石澤通康、槇島誠
    • Organizer
      第35回胆汁酸研究会
    • Place of Presentation
      北海道医療大学札幌サテライトキャンパス(北海道)
    • Related Report
      2013 Research-status Report
  • [Presentation] AF2構造修飾型の新規VDR選択的モジュレーターの合成と生物活性

    • Author(s)
      石澤通康、渡會友祐、前川和樹、工藤健、内田光、伊藤暢聡、常盤広明、山田幸子、槇島誠
    • Organizer
      第8回日本大学先端バイオフォーラム
    • Place of Presentation
      日本大学会館(東京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] ビタミンD受容体パーシャルアゴニストの開発と組織選択的機能発現の可能性

    • Author(s)
      石澤通康、前川和樹、工藤健、中林誠、内田光、伊藤暢聡、常盤広明、山田幸子、槇島誠
    • Organizer
      第524回日大医学会例会
    • Place of Presentation
      日本大学医学部(東京都)
    • Related Report
      2013 Research-status Report
  • [Remarks] 日本大学医学部生化学ホームページ

    • URL

      http://www.med.nihon-u.ac.jp/~biochem/index.html

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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