The mechanism by which statins repress endogenous pathogenic crystal- or needle-like nanomaterial-induced inflammasome activation in macrophages
| Project/Area Number |
17K08406
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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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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インフラマソーム / IL-1beta / NLRP3 / スタチン / コレステロール / カーボンナノチューブ / 薬学 / 脂質 / 炎症 |
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| Outline of Final Research Achievements |
Endogenous and exogenous pathogenic crystals, such as cholesterol crystals, monosodium urate crystals, and asbestos-like multiwall carbon nanotubes (MWCNT) induce inflammasome activation in macrophages. We found that statins repress the crystal-stimulated the NLRP3 inflammasome activation and mature IL-1beta release by inhibiting the internalization of crystals. Various statins exerted the inhibition by decreasing prenyl-intermediates. The scavenger receptor MSR1 partly contributed to MWCNT-stimulated IL-1beta production and statins repressed the expression.
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| Academic Significance and Societal Importance of the Research Achievements |
コレステロールや尿酸など内在性の結晶性異物によるNLRP3インフラマソーム活性化は、動脈硬化や痛風など慢性炎症の病態進展に深く関わる。本研究において、スタチンが顕著な抑制作用を示すことを発見するとともに、インフラマソームを介するスタチンの新しい抗炎症メカニズムが明らかになった。この成果は、MWCNTやアスベスト等の外来性異物が誘発する炎症病態の解明や治療薬創製、健康被害防止に道を拓くものと考えられる。
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Report
(7 results)
Research Products
(7 results)
