Imiquimod-induced skin inflammation is relieved by knockdown of sodium channel Na_x

Na_x is an atypical sodium channel that mediates inflammatory pathways in pathological conditions of the skin. In this study, we developed a skin inflammation model in the rabbit ear through application of imiquimod (IMQ). Knockdown of Na_x using RNAi attenuated IMQ-induced skin inflammation, including skin erythema, scaling and papule formation. Histologic analysis showed that thickening and insufficient differentiation of the epidermis found in psoriasis-like skin were normalized by administration of Na_x -RNAi. Excessive infiltration of inflammatory cells found in inflammatory lesions, such as mast cells, eosinophils, neutrophils, T cells and macrophages, was reduced by Na_x -RNAi. Expression of S100A9, which is a downstream gene of Na_x and a mediator of inflammation, was decreased by Na_x -RNAi. Our results demonstrated that knockdown of Na_x ameliorated IMQ-induced psoriasis-like skin inflammation in vivo. Thus, targeting of Na_x may represent a potential therapeutic option for the treatment of psoriasis.