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Analysis of control mechanism of inflammasome and application to treatment of autoimmune diseases

Research Project

Project/Area Number 16K09923
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionKyushu University

Principal Investigator

HIROKI MITOMA  九州大学, 大学病院, 助教 (60467909)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
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
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2019 2017 2016

All Presentation (3 results)

  • [Presentation] Activation of caspase-1 in CD16-positive monocyte and correlation with disease activity in systemic lupus erythematosus2019

    • Author(s)
      猪口翔一朗,三苫弘喜,河野正太郎,綾野雅宏,木本泰孝,赤星光輝,有信洋二郎,赤司浩一,堀内孝彦,新納宏昭
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血小板は単球のNLRP3 inflammasomeを活性化してIL-1β産生を増強する2017

    • Author(s)
      中野翔太
    • Organizer
      日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ベーチェット病における血小板活性化と単球分画の解析2016

    • Author(s)
      中野翔太
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      横浜
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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