Journal of Inflammation Research
Topical Remibrutinib Attenuates LL37-Induced Rosacea-Like Dermatitis by Inhibiting BTK Activation, NF-κB Signaling and Mast Cell Activation
By Wangchao Li, Huiping Fan, Hua Liu and 4 others.
Abstract
Background
Rosacea is a chronic inflammatory skin disorder in which LL37-driven mast cell activation contributes to cutaneous inflammation. Bruton’s tyrosine kinase (BTK) is a key regulator of canonical IgE-dependent mast cell responses; however, its role in LL37-induced, IgE-independent mast cell activation remains unclear. This study investigated the involvement of BTK activation and nuclear factor-κB (NF-κB) signaling in LL37-induced mast cell activation and evaluated the therapeutic effects of topical remibrutinib in experimental rosacea-like dermatitis.
Methods
Transcriptomic data from rosacea lesions (GSE65914) were analyzed to identify dysregulated inflammatory pathways. LL37-stimulated LUVA mast cells and an LL37-induced mouse model of rosacea-like dermatitis were used for in vitro and in vivo evaluation, respectively. Cell viability, mast cell degranulation, and inflammatory mediator production were assessed using the Cell Counting Kit-8 assay (CCK-8) and enzyme-linked immunosorbent assays (ELISA). Cutaneous inflammation and dermal mast cell accumulation were evaluated by histopathological examination and toluidine blue staining. BTK and NF-κB phosphorylation were examined by Western blotting and immunofluorescence.