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The therapeutic strategy for burn-induced immunosuppression: PPARgamma activation for control of innate immune response

Research Project

Project/Area Number 17K11602
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionNational Defense Medical College

Principal Investigator

MIYAZAKI HIROMI  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 防衛医学研究センター, 助教 (30531636)

Co-Investigator(Kenkyū-buntansha) 齋藤 大蔵  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 防衛医学研究センター 外傷研究部門, 教授 (90531632)
小野 聡  東京医科大学, 医学部, 兼任教授 (30531355)
木下 学  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 免疫・微生物学, 准教授 (70531391)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsマクロファージ / 殺菌活性 / 敗血症 / 自然免疫 / 殺菌作用 / 貪食活性
Outline of Final Research Achievements

Severe burn injury causes the Kupffer cells dysfunction and attenuates the host defense against bacterial infections. Peroxisome proliferator-activated receptor-gamma (PPARγ) is abundantly expressed in macrophages and plays a critical role for regulation of immune responses during the inflammation. We herein investigated the role of PPARγ during the inflammatory response in post-burn bacterial infection.
We reported that pioglitazone, a specific ligand and agonist for PPAR-γ, strongly activates resident Kupffer cells and recruited macrophages in the liver of burn-injured mice. In addition, we found that PPARγ agonist alleviated burn-induced infectious sensitivity and decreased mortality against gram-negative bacterial sepsis via a mechanism dependent on suppressing proinflammatory cytokine production and enhancing bacterial clearance in the liver.

Academic Significance and Societal Importance of the Research Achievements

重度侵襲後には生体防御能が減弱化し易感染性となり、感染症の合併が過剰な炎症や免疫麻痺を引き起こし予後をさらに不良としている。本研究により、炎症反応のみならず食細胞の細菌排除機能を調節する機序を明らかにしたことは、感染症合併を回避・軽減する新たな切り口として、重症病態の治療に関する研究に貢献することが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] The reduced bactericidal activity of neutrophils as an incisive indicator of water-immersion restraint stress and impaired exercise performance in mice2019

    • Author(s)
      Kinoshita M, Nakashima, H, Nakashima M, Koga M, Toda H, Koiwi K, Morimoto Y, Miyazaki H, Saitoh D, Suzuki H, Seki S
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 4662-4662

    • DOI

      10.1038/s41598-019-41077-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Coenzyme Q10 improves susceptibility to methicillin-resistant Staphylococcus aureus bloodstream infection in extensive burned mice by modulating intestinal immunity2019

    • Author(s)
      Miyazaki Hiromi, Kinoshita Manabu, Tomura Satoshi, Seki Shuhji, Saitoh Daizoh
    • Organizer
      第48回日本免疫学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 重症病態におけるミトコンドリアの代謝制御と免疫系への作用2019

    • Author(s)
      宮崎裕美、木下 学、山本 順寛、戸村 哲、関 修司、齋藤 大蔵
    • Organizer
      第33回日本外傷学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] シンポジウム:自然免疫応答の制御による重度侵襲後の敗血症対策2018

    • Author(s)
      宮崎裕美、木下学、戸村哲、関修司、齋藤大蔵
    • Organizer
      第33回日本Shock学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 核内受容体活性化を介した自然免疫調節による重症熱傷後の敗血症対策2018

    • Author(s)
      宮崎裕美、木下学、瀬野宗一郎、関根康雅、戸村哲、関修司、齋藤大蔵
    • Organizer
      第46回日本救急医学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] パネルディスカッション侵襲を制御する:熱傷後の敗血症に対する自然免疫応答制御の有効性2017

    • Author(s)
      宮崎裕美、木下学、関根康雅、瀬野宗一郎、戸村哲、関修司、齋藤大蔵
    • Organizer
      第45回日本救急医学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Coenzyme Q10 supplementation protects against methicillin-resistant Staphylococcus aureus infection in burn-injured mice2017

    • Author(s)
      宮崎裕美、木下学、戸村哲、瀬野宗一郎、関修司、齋藤大蔵
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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