Neuroblast Differentiation-Associated Protein Derived Polypeptides: AHNAK(5758-5775) Induced Inflammatory Reaction in Skin By Mast Cells Activation

Abstract

Psoriasis is a chronic inflammatory skin disease. Mast cells significantly increase and activate in the lesions and are involved in psoriatic inflammation. Neuroblast differentiation-associated protein (AHNAK) mainly express in skin, esophagus and kidney, 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 needs 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 infiltrated in skin and cytokines release in vivo. Release of inflammatory mediators by mouse primary mast cells, LAD2 cells and human neutrophils were measured in vitro. Neutrophils and mast cells were co-cultured to verify AHNAK(5758-5775)’ role in inflammation. Molecular docking analysis, molecular dynamics simulation and siRNA transfection were used to prove the receptor of AHNAK(5758-5775). AHNAK(5758-5775) caused skin inflammation in WT mice by recruitment of neutrophils and cytokines release. Moreover, AHNAK(5758-5775) does not directly activate neutrophils PPD, while it is via mast cells. ST2 seems to be a key receptor meditating the activation effect of AHNAK(5758-5775) on mast cells and lead to cytokines release. Altogether, we proposed the novel polypeptide: AHNAK(5758-5775), which might induce inflammation and participated in the occurrence and development of psoriasis by activating mast cells.