Elucidation of the role of MAPK in atopic dermatitis from the perspective of itch, inflammation, and barrier and therapeutic application

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyushu University
• Principal Investigator: Nakahara Takeshi 九州大学, 医学研究院, 教授 (40529848)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アトピー性皮膚炎 / ERK経路

Outline of Final Research Achievements

We examined the expression of p-ERK in mouse and human AD skin. We also investigated the effects of the topical application of an ERK inhibitor on the dermatitis score, transepidermal water loss (TEWL), histological change, and expression of filaggrin, using an AD-like NC/Nga murine model. The effects of an ERK inhibitor on filaggrin expression in normal human epidermal keratinocytes (NHEKs) and on chemokine production from bone marrow-derived dendritic cells (BMDCs) were also evaluated.
p-ERK was highly expressed in mouse and human AD skin. Topical application of an ERK inhibitor alleviated the clinical symptoms, histological changes, TEWL, and decrease in expression of filaggrin in the AD-like NC/Nga murine model. The ERK inhibitor also restored the IL-4 induced reduction in the expression of filaggrin in NHEK, and inhibited chemokine pro-duction from BMDC induced by IL-4.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

最近のアトピー性皮膚炎治療は、サイトカインをターゲットにした全身治療が数多く登場し、シグナル伝達経路としてはJAK-STAT経路が内服・外用治療のターゲットとなっている。しかし、まだまだ多くの患者さんの症状を消失させるには至っていない。今回、アトピー性皮膚炎の病態との関連が報告されているERK経路の実際の発現を確認し、vivoもしくはvitroの実験で、ERK阻害薬の外用がアトピー性皮膚炎の症状を軽減できる可能性が示唆された。このような新規作用機序の外用薬と既存の治療薬をうまく組み合わせることで、アトピー性皮膚炎のさらなる症状改善につながる可能性が考えられた。