Understanding and chemical control of sterile inflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03371
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Osaka University
• Principal Investigator: saitoh tatsuya 大阪大学, 薬学研究科, 教授 (60456936)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫 / 炎症 / サイトカイン / 細胞死 / オルガネラ / 微粒子

Outline of Final Research Achievements

In Japan, diseases caused by factors unique to modern society (e.g., environmental pollution, excessive nutritional intake, and aging population) have become problematic. The pathogenesis of these diseases is closely related to sterile inflammation induced by the innate immune system that senses irritant particles. In the present study, we analyzed new molecular mechanisms and their control methods related to irritant particle-induced inflammation and obtained the following results (1)-(3). (1) We identified new inflammatory mediators released in response to irritant particles. Then, (2) we elucidated the molecular mechanisms involved in the release of these inflammatory mediators. (3) We identified a compound that potently suppresses inflammation induced by irritant particles and elucidated its mechanism of action. Furthermore, we demonstrated the therapeutic effect of the compound in a mouse model of the irritant particle-induced disease.

Free Research Field

生物系薬学、免疫学

Academic Significance and Societal Importance of the Research Achievements

病原体の成分を感知するパターン認識受容体を介したサイトカイン・インターフェロン放出の発見は、病原体に対する多様な炎症応答の分子実態解明へとつながってきた。一方で、微粒子に対する炎症応答の根本を成す分子機構はなにか？という問いにはまだ十分な答えが無い状況にある。本研究はこの重要な問いに答えるという点で学術的な意義がある。また、本研究は微粒子が誘導する炎症を抑制するためにはどのような分子を標的とすることが最も効果的なのか？という問いに答え、新たな機序で働く抗炎症薬の開発基盤を整えるという点で社会的な意義がある。