Elucidation of NLRP3 inflammasome regulation mechanism by E3 ubiquitin ligase

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07055
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Jichi Medical University
• Principal Investigator: Kamata Ryo 自治医科大学, 医学部, ポスト・ドクター (60801420)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 循環器 / 免疫学 / ユビキチン

Outline of Final Research Achievements

Sterile inflammation is involved in the pathogenesis of cardiovascular diseases such as arteriosclerosis and myocardial infarction. Recent investigations have suggested that sterile inflammation is mediated by NLRP3 inflammasome. Elucidating the regulatory mechanism of NLRP3 inflammasome is expected to lead to the development of new therapeutic methods. However, its regulatory mechanism is still unknown. In this study, we focused on ARIH2, an E3 ubiquitin ligase newly identified from the NLRP3 inflammasome complex, and revealed that ARIH2 ubiquitinated NLRP3 and regulated the expression level of NLRP3 via proteasomal degradation.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、ARIH2がNLRP3の発現量を調節して炎症を制御していることを明らかにした。これまでに、NLRP3インフラマソームは心血管疾患のみならず、無菌性炎症が関わる多くの疾患の発症機構に関与することから、ARIH2によるNLRP3インフラマソームの制御機構の一端を明らかにしたことは、インフラマソームが関与する様々な疾患の病態解明や治療法開発にも大きく貢献することが期待される。