The therapeutic strategy for burn-induced immunosuppression: PPARgamma activation for control of innate immune response
Project/Area Number |
17K11602
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Emergency medicine
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Research Institution | National 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)
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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)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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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)
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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.
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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。
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Report
(4 results)
Research Products
(7 results)
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[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
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 4662-4662
DOI
Related Report
Peer Reviewed / Open Access
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