2018 Fiscal Year Final Research Report
Analysis of localization and function of glucocorticoid receptor as a therapeutic target for eosinophilic airway inflammation
| Project/Area Number |
16K08951
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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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| Research Field |
Laboratory medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
神田 晃 関西医科大学, 医学部, 講師 (70375244)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | ステロイド受容体 / 好酸球 / 好酸球性副鼻腔炎 / 喘息 / ホスファターゼ / ステロイド感受性 |
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| Outline of Final Research Achievements |
We found that the expressions of functional glucocorticoid receptor (GRα) and phosphatases associated with the ability of GR nuclear translocation were significantly reduced in mucosa from inflammatory site compared with normal mucosa from the same patients with eosinophilic airway inflammation. Excessive production of inflammatory mediators such as innate immune response inducible cytokines and eosinophil chemokines caused by impairment of GR function, or reduction of corticosteroid sensitivity, in the inflammatory site may prolong eosinophilic inflammation. On the other hand, activation and overexpression of protein phosphatase PP2A in the inflammatory site could be a therapeutic strategy for corticosteroid insensitivity.
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| Free Research Field |
好酸球性気道炎症
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| Academic Significance and Societal Importance of the Research Achievements |
難治性好酸球性気道炎症の代表格である喘息合併好酸球性副鼻腔炎におけるステロイド感受性の低下のメカニズムを解明することは、難病に指定されている本疾患の病勢コントロールをする上で非常に重要である。同一患者においてステロイド受容体機能の低下に関与する分子の発現異常が正常粘膜部位と比較して炎症局所で顕著に見られたことから、治療ターゲットがより明確になり、新しい治療法（治療薬およびその炎症局所への送達方法）の開発につながることが多いに期待できる。
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