2. Academic Validation
  3. CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis

  • Eur J Immunol. 2023 Jul 7;e2350374. doi: 10.1002/eji.202350374.
Jiajia Tong 1 2,  Yan Li 1,  Xiaojie Cai 1,  Fangzhou Lou 1,  Yang Sun 1,  Zhikai Wang 1,  Xichen Zheng 1,  Hong Zhou 1,  Ziyang Zhang 3,  Zilong Fang 4,  Wenxiang Ding 1,  Siyu Deng 1,  Zhenyao Xu 1,  Xiaoyin Niu 2,  Honglin Wang 1
Affiliations

Affiliations

  • 1 Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
  • 2 Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, P. R. China.
  • 3 School of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
  • 4 Medical School, Kunming University of Science and Technology, Kunming, P. R. China.
PMID: 37417726 DOI: 10.1002/eji.202350374
Abstract

Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK Activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.

Keywords

cellular immunology; dermatology; immune responses; mast cells; skin diseases/immunology.

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