Analysis of control mechanism of inflammasome and application to treatment of autoimmune diseases
| Project/Area Number |
16K09923
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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 |
Collagenous pathology/Allergology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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)
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| Keywords | 自己免疫疾患 / マクロファージ / インフラマソーム / 関節リウマチ / ヒドロキシクロロキン / 単球 / IL-1β / CD16陽性単球 / IL-18 / 慢性炎症性疾患 / 免疫学 |
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| Outline of Final Research Achievements |
Human CD16-positive monocytes had high ability to secrete active form of IL-1β. Secretion of active IL-1β from peripheral blood monocytes after LPS stimulation was higher in rheumatoid arthritis (RA) with high disease activity compared to healthy controls, because CD16 positive monocytes were increased in active RA. The suppressive reagents for IL-1 β secretion was examined. Colchicine inhibited IL-1β secretion from LPS-stimulated monocytes at high concentrations. Hydroxychloroquine also suppressed IL-1β secretion from LPS stimulated monocytes. There was no extracellular release of the cytoplasmic components of monocytes and no cell death was observed. Therefore, it was considered that the secretion of active IL-1β from monocytes was mediated by a different pathway from pyroptosis in macrophages.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの自己免疫疾患におけるインフラマソームの病態形成への役割は明らかとなっていない。今回我々は関節リウマチの単球において、インフラマソーム経路が活性化していることを明らかにした。また現在全身性エリテマトーデスの治療薬として使用されているヒドロキシクロロキン（HCQ）はインフラマソームの活性化を抑制することを見出した。インフラマソームの関与が想定される病態、疾患においてHCQが有用である可能性が示唆された。
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Report
(4 results)
Research Products
(3 results)
