2023 Fiscal Year Final Research Report
CYP27A1: A novel target for treatment of asthma
| Project/Area Number |
21K08147
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 気管支喘息 / 27-hydroxycholesterol / CYP27A1 / nilvadipine / ダニ抗原 / 上皮バリア機能 / 好中球性炎症 / PAR2 |
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| Outline of Final Research Achievements |
This study aimed to elucidate the contribution of CYP27A1 and 27-hydroxycholesterol (27-HC) to the pathophysiology of asthma. The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin. The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.
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| Free Research Field |
呼吸器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では新たな分子機構としてCYP27A1と27-hydroxycholesterol (27-HC)の産生経路に着目して喘息の新規病態の解明を試みた。動物モデルではこの経路が好酸球性のみならず好中球性気道炎症にも関与すること、培養細胞実験では上皮バリア機能の破綻に関与することを見出した。現在日常臨床で使用されている降圧薬のnilvadipineがダニ抗原誘導性の気道炎症を抑制したことは特筆すべき結果であり、本研究において気管支喘息の新たな治療標的を見出したこと、nilvadipineの有用性が示唆されたことで今後の難治性喘息の新たな治療法の開発に貢献できると考えられる。
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