Effect of endothelin-1 on prutitus and inflammarion of atopic dermatitis

• Project/Area Number: 17K10247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kyushu University
• Principal Investigator: Nakahara Makiko 九州大学, 医学研究院, 助教 (80530120)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アトピー性皮膚炎 / かゆみ / エンドセリン

Outline of Final Research Achievements

We hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, scratching bouts, and serum level of thymus and activation‐regulated chemokine in NC/Nga mice. Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions.
EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎（AD）は非常に頻度の高い疾患の一つであり、ADの発症や病態には複数の因子が互いに影響を及ぼしあい複雑に関与している。ET-1は元来血管収縮作用のある物質として発見されたペプチドで、ADの発症や炎症などへのET-1の関与についてはこれまでほとんど報告されてこなかったが、今回の成果からET-1がADの病態へ深く関与していることが推測された。今後は、治療薬の開発など臨床応用も期待され、ADだけでなく、AD以外の炎症やかゆみを伴う疾患での応用にも広く寄与できる可能性がある。