Clarification of the role of DAMP in health effects caused by particulate matters and risk assessment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03038
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: University of Fukui
• Principal Investigator: Hiraku Yusuke 福井大学, 学術研究院医学系部門, 教授 (30324510)
• Co-Investigator(Kenkyū-buntansha): 田中 昭代 九州大学, 医学研究院, 講師 (10136484) ; 村田 真理子 三重大学, 医学系研究科, 教授 (10171141) ; 中野 真規子 慶應義塾大学, 医学部(信濃町), 講師 (70384906)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 粒子状物質 / 炎症 / DAMP / インジウム / リスク評価

Outline of Final Research Achievements

Particulate matters are accumulated in the respiratory systems by inhalation exposure and induce chronic inflammation, leading to carcinogenesis and fibrosis. DAMPs include molecules that are released from damaged cells to mediate inflammatory responses, such as HMGB1 and S100 family proteins. This study provided a new mechanism by which indium compounds induce DNA damage in human lung epithelial cells via the release of HMGB1 from exposed cells and inflammatory responses in neighboring cells. In lung tissues of indium-exposed rats, the expression levels of S100 family proteins were dramatically elevated. In workers with past indium exposure, serum indium and KL-6 levels remain to be high, raising concerns about the risk of lung carcinogenesis in the future. DAMP, including HMGB1 and S100 family proteins, may be used for evaluation of the risk of diseases caused by particulate matters.

Free Research Field

衛生学、公衆衛生学、環境医学、産業医学

Academic Significance and Societal Importance of the Research Achievements

本研究では、我々の実験研究により報告した粒子状物質による健康障害の新規分子機構に基づき、炎症反応に重要な役割を果たすDAMPに注目して、従来と全く異なる発想に基づくバイオマーカーの開発を目指す点に学術的意義および社会的意義がある。また、基礎研究および疫学研究の成果を基盤として、ヒト集団における産業化学物質による健康影響のリスク評価に発展させ、労働者の健康管理に寄与する点に創造性がある。