ID | 67018 |
フルテキストURL | |
著者 |
Sasakura, Minori
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Urakami, Hitoshi
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Tachibana, Kota
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Ikeda, Kenta
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Hasui, Ken-Ichi
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Matsuda, Yoshihiro
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Sunagawa, Ko
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Ennishi, Daisuke
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Tomida, Shuta
Center for Comprehensive Genomic Medicine, Okayama University Hospital
Kaken ID
researchmap
Morizane, Shin
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
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抄録 | Background: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders.
Methods: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines. Results: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not.Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity. Conclusions: Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors. |
キーワード | AP-1 inhibitor
Atopic dermatitis
Baricitinib
T-5224
Topical application
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発行日 | 2024-04
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出版物タイトル |
Allergology International
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巻 | 73巻
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号 | 2号
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出版者 | Japanese Society of Allergology
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開始ページ | 323
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終了ページ | 331
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ISSN | 1323-8930
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NCID | AA11091750
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2024 Japanese Society of Allergology.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1016/j.alit.2023.12.006
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ライセンス | http://creativecommons.org/licenses/by-nc-nd/4.0/
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