Abstract
Atopic dermatitis (AD) is a chronic eczematous skin disease associated with intense pruritus and skin barrier dysfunction. Not only histamine, but also various pruritogens can induce itch in the skin of AD patients. Among them, one of the potentially endogenous pruritogens in the skin is endothelin-1 (ET-1). To understand the mechanism of action, production, and roles of ET-1 in the skin of AD, we reviewed recent advances in the understanding of ET-1. Recently, functions of ET-1 related to inflammation other than itch have been reported. The expression of ET-1 and IL-25 was found to be coordinately upregulated in the lesional skin of AD patients and a murine AD model. IL-25 augmented ET-1 expression, and ET-1 reciprocally increased IL-25 expression in keratinocytes. In addition, ET-1 directly induced phenotypic and functional maturation of murine bone marrow–derived dendritic cells (DCs) and modified T cell responses. ET-1 might be involved not only in pruritus but also in inflammation of AD. ET-1 may be a future target for antipruritic and anti-inflammatory agents in AD treatment.
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