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Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF\u2010\u03b1\u2010stimulated HaCaT cells and DNCB\u2010induced Balb\/c mice as in\u00a0vitro and in\u00a0vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL\u20104, IL\u201013, TNF\u2010\u03b1, IL\u20105, IL\u201031, IL\u201033, IgE, TSLP, IL\u201017, IL\u201023, IL\u20101\u03b2, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF\u2010\u03b1\u2010induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi\u20101 (a mitochondrial fission inhibitor) and Ezrin\u2010specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co\u2010immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin\u2010mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.18375","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T01:41:11Z","timestamp":1721698871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Celastrol alleviates atopic dermatitis by regulating Ezrin\u2010mediated mitochondrial fission and fusion"],"prefix":"10.1111","volume":"28","author":[{"given":"Dandan","family":"Wang","sequence":"first","affiliation":[{"name":"Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases Yanbian University  Yanji China"},{"name":"Department of Anatomy, Histology and Embryology Yanbian University Medical College  Yanji 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