Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis

Autor: Minori Sasakura, Hitoshi Urakami, Kota Tachibana, Kenta Ikeda, Ken-ichi Hasui, Yoshihiro Matsuda, Ko Sunagawa, Daisuke Ennishi, Shuta Tomida, Shin Morizane
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Allergology International, Vol 73, Iss 2, Pp 323-331 (2024)
Druh dokumentu: article
ISSN: 1323-8930
DOI: 10.1016/j.alit.2023.12.006
Popis: 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
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