Dermcidin-derived polypeptides: DCD(86-103) induced inflammatory reaction in the skin by activation of mast cells via ST2.

BACKGROUND: Psoriasis is a chronic inflammatory disease. Mast cells are significantly increased and activated in the lesions of patients with psoriasis, contributing to psoriatic inflammation. Dermcidin (DCD) is a natural antibacterial peptide secreted by sweat glands and is usually transported to the epidermal surface by sweat. Whether DCD is involved in mast cell activation remains unclear and the mechanisms by which DCD is involved in skin inflammatory reactions require further investigation. METHODS: We investigated whether dermcidin-derived polypeptides DCD(86-103) activate mast cells and induce skin inflammatory reactions that contribute to psoriasis. Wild-type mice were treated with DCD(86-103) to observe the inflammatory reactions in the skin and cytokine release in vivo. The release of inflammatory mediators by mouse primary mast cells and LAD2 cells was measured in vitro. Molecular docking analysis, molecular dynamics simulation, and siRNA transfection were used to identify DCD(86-103). RESULTS: DCD(86-103) caused a skin inflammatory reaction in wild-type mice via cytokine release. Moreover, DCD(86-103) directly activated mast cells and induced cytokine release in vitro. ST2 may be a key receptor that mediates the activation effect of DCD(86-103) on mast cells leading to cytokine release. CONCLUSION: DCD(86-103) may have induced an inflammatory reaction and participated in the occurrence and development of psoriasis.