| Project/Area Number |
18K08300
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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 53050:Dermatology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 乾癬 / エンドセリンー1 / 樹状細胞 / エンドセリン-1 / エンドセリンー１ / アトピー性皮膚炎 / サイトカイン |
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| Outline of Final Research Achievements |
The role of the interaction between ET-1 and ET-1 receptors in the pathogenesis of psoriasis remains elusive. In this study, we investigated the effects of ET-1 receptor antagonist on imiquimod (IMQ) -induced psoriasiform dermatitis in mouse. Psoriasis-related cytokines such as IL-17A and TNF-α induced ET-1 expression in human keratinocytes. Topical application of selective endothelin A receptor (ETAR) antagonist ambrisentan significantly attenuated the development of IMQ-induced psoriasiform dermatitis and also significantly inhibited the histological inflammation and cytokine expression (TNF-α, IL-12p40, IL-12 p19, and IL-17) in the lesional skin of the mouse model. Furthermore, topical
application of ambrisentan suppressed phenotypic and functional activation of dendritic cells in lymph nodes. Our findings indicate that the ET-1 and ETAR axis plays an important role in the pathogenesis of psoriasis and is a potential therapeutic target for treating psoriasis.
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| Academic Significance and Societal Importance of the Research Achievements |
現在乾癬の外用治療はステロイド外用薬が中心であり、どうしても長期外用にて局所的ではあるが皮膚萎縮などの副作用が出現しうる。そこで、異なる機序の外用薬を開発することで、治療効果向上に加えて、副作用の軽減も期待できる。今回エンドセリン-1という新たなターゲットの外用治療が病態を改善しうることが示され、より治療選択肢が拡がる可能性が示された。
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