Role of extracellular HMGB1 in promotion of inflammation
| Project/Area Number |
18K07167
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49070:Immunology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yanai Hideyuki 東京大学, 先端科学技術研究センター, 特任准教授 (70431765)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HMGB1 / 自然免疫 / 腫瘍 / 炎症 / 好中球 / DAMPs / 自然免疫受容体 / がん / 死細胞 |
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| Outline of Final Research Achievements |
In this study, we examined the mechanism of how HMGB1 promotes neutrophil migration and the importance of HMGB1 in the pathogenesis of inflammatory diseases. Interestingly, administration of HMGB1-targeting inhibitor ISM ODN into ConA-treated mice suppressed liver inflammation and neutrophil infiltration. ISM ODN treatment also reduced B16F10 tumor growth, suggesting that the promotion of neutrophil infiltration by HMGB1 augments the liver inflammation and tumor growth. To further study HMGB1-induced neutrophil migration in vivo, we generated knock-in mice that constantly release HMGB1 extracellularly.
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| Academic Significance and Societal Importance of the Research Achievements |
HMGB1は炎症疾患病態を増悪するDAMPsの代表的な分子の一つとして捉えられている。HMGB1に対する阻害剤や中和抗体が多数作成され、実際に種々の病態を抑制することも報告されているが、HMGB1が実際にどのように炎症を促進しているのか、そのメカニズムには未だ不明な点が多い。本研究の結果から、HMGB1は好中球の遊走を介して炎症を促進する可能性が示唆された。実際、HMGB1を阻害すると、マウス肝炎モデルおよび腫瘍モデルにおいて好中球の炎症部位への浸潤が阻害された。HMGB1を標的とした治療法の開発において、好中球の割合が指標になる可能性が示唆された。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] HMGB1-mediated chromatin remodeling attenuates Il24 gene expression for the protection from allergic contact dermatitis2021
Author(s)
Senda N, Yanai H, Hibino S, Li L, Mizushima Y, Miyagaki T, Saeki M, Kishi Y, Hangai S, Nishio J, Sugaya M, Taniguchi T, Sato S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 118
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis.2019
Author(s)
Negishi H, Endo N, Nakajima Y, Nishiyama T, Tabunoki Y, Nishio J, Koshiba R, Matsuda A, Matsuki K, Okamura T, Negishi-Koga T, Ichinohe T, Takemura S, Ishiwata H, Iemura SI, Natsume T, Abe T, Kiyonari H, Doi T, Hangai S, Yanai H, Fujio K, Yamamoto K, Taniguchi T.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 116
Issue: 47
Pages: 23653-23661
DOI
Related Report
Peer Reviewed / Open Access
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