Development of airway epithelial keratinization and barrier function as a novel therapeutic target for asthma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16308
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Showa University
• Principal Investigator: Inoue Hideki 昭和大学, 医学部, 兼任講師 (80813162)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 気道上皮細胞 / 角層蛋白 / 気管支喘息

Outline of Final Research Achievements

Epithelial barrier dysfunction is implicated in asthma. We investigated the effects of fungal exposure on airway epithelial cells. Gene and protein expression were examined in the airway epithelial cell line 16HBE14o- after exposure to alternaria extract. RNA-Seq revealed upregulation of RNA regulation and transcription-related genes upon alternaria exposure. Downregulation of genes related to cell membrane function of intracellular organelles was observed. Alternaria exposure induced upregulation of the inflammatory cytokines IL-6 and IL-8, and downregulation of the filaggrin, a keratinocyte protein. Treatment with JTC-801 did not improve filaggrin expression. Control of fungal exposure-induced airway inflammation and maintenance of the keratinocyte protein barrier may be involved in the improvement of the pathophysiology of fungal sensitization asthma.

Free Research Field

気管支喘息

Academic Significance and Societal Importance of the Research Achievements

気管支喘息は成人の5-9%が罹患する疾患であり、コントロール不良は社会経済的な損失を招く。近年、真菌感作が喘息悪化に深く関与することが示唆されており、その病態解明が重要課題となっている。本研究では、真菌曝露が気道上皮細胞に及ぼす影響を網羅的に解析し、真菌感作喘息の病態解明に新たな視点を与えることを目的とした。気道上皮細胞株16HBE14o-にアルテルナリア抽出液を曝露し、遺伝子発現解析、炎症性サイトカイン測定、角層蛋白発現解析を行った。真菌曝露により、炎症性サイトカインの放出と角層蛋白の減少、細胞膜機能の低下が認められた。これらの異常は、気道炎症の悪化と気管支喘息の発症に寄与する可能性がある。