LB873 Neuroblast differentiation-associated protein derived polypeptides: AHNAK(5758-5775) induced inflammatory reaction by activation mast cells via ST2

Mast cells significantly increase and activate in psoriasis lesions and are involved in psoriatic inflammation. Neuroblast differentiation-associated protein (AHNAK) mainly express in skin, esophagus, kidney and other organs, which participates in the differentiation of neurons, the formation of cytoskeletal structure muscular regeneration, and the calcium homeostasis process. Whether AHNAK is involved in mast cell activation is unclear, and the mechanisms of AHNAK-induced skin inflammation also need investigation. To investigate whether Neuroblast differentiation-associated protein derived polypeptides: AHNAK(5758-5775) activates mast cells and induces skin inflammation contributing to psoriasis. Wild-type mice were treated with AHNAK(5758-5775) to observe inflammatory cells infiltration in skin and cytokines release in vivo. Release of inflammatory mediators by mouse primary mast cells and LAD2 cells were measured in vitro. The receptor of AHNAK(5758-5775) was demonstrated by molecular docking analysis, molecular dynamics simulation and siRNA transfection. AHNAK(5758-5775) could cause skin inflammatory reaction and induce cytokines release in WT mice, and could activate mast cells in vitro. ST2 may be a key receptor mediating the activation effect of AHNAK(5758-5775) on mast cells and leading to cytokine release. AHNAK(5758-5775) might induce inflammatory reaction and participate in the onset and development of psoriasis.