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The role of neuromodulatory factors in innate immune system

Research Project

Project/Area Number 16K08148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionNational Agriculture and Food Research Organization

Principal Investigator

TAKENOUCHI Takato  国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門, 主席研究員 (20292518)

Co-Investigator(Kenkyū-buntansha) 月本 光俊  東京理科大学, 薬学部薬学科, 准教授 (70434040)
Research Collaborator IWAMARU Yoshifumi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords自然免疫応答 / 神経調節因子 / マクロファージ / 非典型的分泌機構 / 細胞応答
Outline of Final Research Achievements

We investigated the secretory mechanisms of DBI and MANF from macrophage-lineage cells, and evaluated the immunomodulatory functions of these neuromodulatory factors in innate immune system. It was demonstrated that DBI and MANF are secreted from macrophages via P2X7 receptor-mediated unconventional secretion pathway. We also established the production system for recombinant proteins of DBI and MANF using Brevibacillus expression system. These factors are produced as secreted proteins in the culture supernatant of brevibacillus transformants. Based on the actions of recombinant MANF in macrophages, we propose the idea that MANF plays an anti-inflammatory role in mice.

Academic Significance and Societal Importance of the Research Achievements

本研究では、神経系の調節因子として知られていたジアゼパム結合阻害因子(DBI)と中脳アストロサイト由来神経栄養因子(MANF)の生体内での役割について、神経系における作用だけでなく、自然免疫系においても調節因子として機能している可能性を示した。また、ブレビバチルス菌を用いた組換え蛋白質作製法が、両因子の分泌型蛋白質を生産するために非常に有効であることを初めて示した。組換えMANFに抗炎症性の作用が認められたことから、その産生・分泌に関わる制御機構が、抗炎症薬など薬剤開発のための新たなターゲットとなる可能性が考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results)

  • [Journal Article] Immortalization and Characterization of Porcine Macrophages That Had Been Transduced with Lentiviral Vectors Encoding the SV40 Large T Antigen and Porcine Telomerase Reverse Transcriptase2017

    • Author(s)
      Takenouchi Takato、Kitani Hiroshi、Suzuki Shunichi、Nakai Michiko、Fuchimoto Dai-ichiro、Tsukimoto Mitsutoshi、Shinkai Hiroki、Sato Mitsuru、Uenishi Hirohide
    • Journal Title

      Frontiers in Veterinary Science

      Volume: 4 Pages: 1-9

    • DOI

      10.3389/fvets.2017.00132

    • NAID

      120006626771

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] マクロファージの簡便な大量回収法とその利用2016

    • Author(s)
      竹之内敬人、吉岡 都、木谷 裕、山中典子
    • Journal Title

      ケミカルエンジニヤリング

      Volume: 61 Pages: 510-515

    • Related Report
      2016 Research-status Report
    • Acknowledgement Compliant
  • [Presentation] 腎マクロファージにおけるP2X7受容体活性化による免疫調節因子の放出2018

    • Author(s)
      箱田公樹、竹之内敬人、木谷裕、月本光俊
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ブタマクロファージ不死化細胞株の樹立と特性解析2018

    • Author(s)
      竹之内敬人、木谷裕、鈴木俊一、中井美智子、淵本大一郎、月本光俊、新開浩樹、佐藤充、上西博英
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腎マクロファージにおけるP2X7受容体活性化による免疫調節因子の放出2017

    • Author(s)
      箱田公樹、竹之内敬人、木谷裕、月本光俊
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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