Enoximone alleviates atopic dermatitis-like skin inflammation via inhibition of type 2 T helper cell development.

Autor: Song JY; College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea., Lee YJ; College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea., Lee SH; College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea., Lee JY; College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea. Electronic address: jylee98@cau.ac.kr.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113189. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1016/j.intimp.2024.113189
Abstrakt: Atopic dermatitis (AD) is an inflammatory skin disease that affects approximately 15-20 % of the children and 1-3 % of the adults worldwide. Corticosteroids and calcineurin inhibitors are used in AD therapy; however, they cause various side effects. Current studies focus on novel therapeutic targets such as phosphodiesterases (PDEs) to mitigate AD. However, the relationship between PDE3 inhibitors and AD has not yet been reported. This study aimed to investigate the therapeutic effects and pharmaceutical mechanisms of enoximone (Enox), a PDE3 inhibitor. Mice were stimulated with 2,4-dinitrochlorobenzene (DNCB) to induce AD-like skin inflammation and were topically treated with Enox for 2 weeks. Treatment with Enox reduced the dermatitis score, skin water loss, IgE production, and expression of cytokines and chemokines that were elevated by DNCB. Histologically, Enox treatment reduced the skin thickness and the infiltration of various inflammatory cells, including macrophages, mast cells, eosinophils, and type 2 T helper (Th2) cells. HuT78, a human T cell line, was used to investigate the differentiation of T cells into Th2 cells. Enox treatment decreased the expression of Th2 cytokines and GATA3, a Th2 cell marker in HuT78, and suppressed signaling pathways that play a crucial role in Th2 cell differentiation. Collectively, the results demonstrate that Enox alleviates AD-like skin inflammation by inhibiting T-cell development. Thus, Enox may be a therapeutic candidate for the treatment of AD.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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