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Topical Application of JAK1/JAK2 Inhibitor Momelotinib Exhibits Significant Anti-Inflammatory Responses in DNCB-Induced Atopic Dermatitis Model Mice

1
Division of Dermatology, Department of Clinical Medicine, Medical College of Yanbian University, Yanji 133000, China
2
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 3973; https://doi.org/10.3390/ijms19123973
Received: 7 November 2018 / Revised: 3 December 2018 / Accepted: 5 December 2018 / Published: 10 December 2018
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
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Abstract

Atopic dermatitis (AD) is a chronic recurrent skin disease dominated by T-helper 2 inflammation. Momelotinib (MMB) is a novel JAK1/JAK2 inhibitor suppressing the signal transduction of multiple pro-inflammatory cytokines. Recent studies indicated that JAK inhibitor could play a therapeutic role in AD disease. In this study, we evaluated the efficacy of MMB as a novel JAK1/JAK2 inhibitor in DNCB-induced AD mice and TSLP-activated dendritic cells. Our data showed that topical application of MMB reduced the skin severity scores and total serum IgE levels, and alleviated the histological indexes including epidermal thickness measurement and mast cell number. Also, it was demonstrated that MMB down-regulated the mRNA expression of IL-4, IL-5, IFN-γ and TSLP, and inhibited the phosphorylation of STAT1, STAT3 and STAT5 in skin lesions. Moreover, MMB reduced the expression of CD80, CD86, MHCII and mRNA of OX40L in TSLP-activated dendritic cells. In general, our study suggests that MMB can improve the symptoms of AD and topical application of MMB can become a promising new therapy strategy for AD. View Full-Text
Keywords: momelotinib; atopic dermatitis; cytokine; DNCB; dendritic cell; JAK/STAT pathway momelotinib; atopic dermatitis; cytokine; DNCB; dendritic cell; JAK/STAT pathway
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Jin, W.; Huang, W.; Chen, L.; Jin, M.; Wang, Q.; Gao, Z.; Jin, Z. Topical Application of JAK1/JAK2 Inhibitor Momelotinib Exhibits Significant Anti-Inflammatory Responses in DNCB-Induced Atopic Dermatitis Model Mice. Int. J. Mol. Sci. 2018, 19, 3973.

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