Elucidation of the pathogenic mechanism of chronic inflammation based on AGE-induced cytokine trapping

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14969
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Shujitsu University
• Principal Investigator: Watanabe Masahiro 就実大学, 薬学部, 講師 (10758246)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 終末糖化産物 / AGEs / 炎症性サイトカイン / 相互作用 / 慢性炎症

Outline of Final Research Achievements

It has been suggested that chronic inflammation may be involved in the pathogenesis of metabolic syndrome, which is thought to be caused by aging and lifestyle. As the cause of chronic inflammation, we have focused on advanced glycation end products (AGEs) generated and accumulated in vivo, and have found that AGEs bind to proinflammatory cytokines, that affect their effects (AGE-induced cytokine trapping). In the present study, we succeeded in (1) constructing a cell analysis system that contributes to the elucidation of the mechanism of cytokine trapping, (2) identifying novel cytokines involved in this phenomenon, and (3) discovering that AGEs activate the action of the identified cytokine.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究において構築した，AGEsによるサイトカイントラッピングの解析系は，本現象のメカニズム解析のみならず，阻害薬探索等にも応用できる可能性が考えられる．また，本研究では，AGEsと相互作用する可能性を有する新規サイトカイン類を複数見出すことに成功している．今後，これらのサイトカイン類の機能にAGEsが与える影響を解析することにより，生体内におけるAGEsの新規作用メカニズムとしてサイトカイントラッピングという現象を位置づけるための手がかりが得られると考える．さらに，これらの解析結果は，慢性炎症が基盤となる病態の新規治療法の開発に寄与することが期待できる．