The crosstalk between hypoxic reaction system and IFNbeta-1a signal at the control of vascular endothelial barrier function

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08877
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: The Tazuke Kofukai
• Principal Investigator: Adachi Takehiko 公益財団法人田附興風会, 医学研究所 第9研究部, 部長 (90252428)
• Co-Investigator(Kenkyū-buntansha): 広田 喜一 関西医科大学, 医学部, 教授 (00283606)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 急性呼吸窮迫症候群 / interferonβ-1a / 細胞間バリア機能 / CD73 / 低酸素誘導性因子 / CD39

Outline of Final Research Achievements

We investigated the role of IFNβ-1a in inducing CD73 expression and its effect on junction proteins. IFNβ-1a increased CD73 expression in endothelial cells in a time- and dose-dependent manner. IFNβ-1a reduced intercellular permeability, and the effect was mediated by both CD73 activity and expression. We found that effect of IFNβ-1a was mediated by both CD73 activity and expression and that IFNβ-1a regulates the localization of junctional proteins and cytoskeletal remodeling in a CD73-dependent manner and that IFNβ-1a increased the expression of junctional proteins, which are important for barrier function maintenance. Analysis using adenosine and an inhibitor of CD73 enzymatic activity suggested that the protective effect of IFNβ-1a on barrier function may be mediated through an adenosine-independent pathway.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

全身炎症の拡大が急性呼吸窮迫症候群(Acute Respiratory Distress Syndrome: ARDS)を含んだ多臓器不全の引き金を引く。一旦発生したARDSの治療は困難であり，治療薬もステロイド剤の使用などが試みられてきたが限定された効果のみしか得られていないという現状がある。本研究はIFNβ-1a製剤が血管内皮の細胞間バリア機能を強化することでこの病態の改善につながる可能性をしめした。この観点で、医学的・社会的な意義があると考えられる。