Abstract Celastrol, a bioactive compound from Tripterygium wilfordii Hook F, has been reported to exert potent anti-inflammatory effects through multiple signaling pathways. While its activity has been studied in various cell types and disease models, its effects in atopic dermatitis (AD) is limited to a few studies in mouse models and remains largely unexplored in in vitro cell models. In this study, anti-inflammatory effects of celastrol were assessed in Th1-driven 2D inflammation models of HaCaT keratinocytes and dermal fibroblasts (DF), and in a Th2-driven 3D AD skin model. Cytokine stimulation mimicked chronic inflammation. Celastrol was applied at sub-cytotoxic concentrations, and inflammatory markers were quantified on the mRNA (qPCR) and protein (ELISA) level. In 2D models, celastrol reduced interleukin (IL)-8 and IL-6 secretion in a concentration-dependent manner, with fibroblasts producing higher cytokine levels than keratinocytes. In 3D AD models, topical celastrol (10 µM) was well tolerated and markedly reduced secretion of IL-8, IL-6, IL-1α, and mRNA expression of CXCL8 , IL6 , IL1B , and IL23A , even under continuous Th2 stimulation. AD biomarker genes CCL26 , CA2 , and NELL2 were unaffected, likely due to persistent cytokine exposure. Celastrol displayed strong anti-inflammatory activity in both Th1- and Th2-driven in vitro skin inflammation models, including a physiologically relevant 3D AD model. Its multitarget action support its potential as a topical treatment candidate for chronic inflammatory skin diseases.
Reddersen et al. (Thu,) studied this question.