| Project/Area Number |
16K08934
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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 |
Laboratory medicine
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| Research Institution | Kobe University |
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Principal Investigator |
KOMAI Koichiro 神戸大学, 保健学研究科, 准教授 (40304117)
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| Project Period (FY) |
2016-10-21 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | インフラマソーム / ASC/PYCARD / 自然免疫 / スプライシング / IL-1 / 自己炎症症候群 / 認知症 / 生活習慣病 / PYCARD/ASC / 自己炎症性疾患 / スプライスバリアント / 回帰性リウマチ / 炎症性疾患 |
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| Outline of Final Research Achievements |
In this study, we performed functional analysis of PYCARD/ASC variant form lacking exon 2 (delta ASC), which is one of the proteins that make up the inflammasome in order to use it as a general-purpose biomarker for autoinflammatory syndromes. As the results, while it was found that the amount of active IL-1β was significantly elevated in the case with delta ASC as compared with wild type by stimulation with monosodium urate, it was decreased in the case with delta ASC as compared with wild type by stimulation with flagellin. Furthermore, as the results of immunoprecipitation experiments, while it was found that the binding capacity of delta ASC for NLRP 3 was increased as compared with wild type upon monosodium urate stimulation, the binding capacity of delta ASC for NLRC4 was decreased as compared with wild type upon flagellin stimulation. We also found that rs8056505 SNP affects the splicing of PYCARD/ASC, but it was also suggested that other factors affect the splicing.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではが炎症シグナル伝達に働くタンパク質複合体「インフラマソーム」の構成分子であるexon2欠損型ASCスプライスバリアントが機能変化をきたしていることを明らかにした。ASCは感染体やアミロイド、コレステロールなど様々な危険因子を受容するNLRP3などによって構成される様々なインフラマソーム共通のアダプター分子として機能し、感染症、認知症や生活習慣病など幅広い疾患を含む「自己炎症症候群」の発症に関与していると考えられることから、本分子が新たな疾患診断のための汎用バイオマーカーとして有効であることが明らかとなった。
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