The role of a-melanocyte-stimulating hormone in cutaneous biology

Abstract

α-Melanocyte stimulating hormone is a neuroimmunomodulating peptide that was recently detected in many non-pituitary tissues including the skin. Accordingly, epidermal cells such as keratinocytes and melanocytes (as well as dermal cells such as fibroblasts and endothelial cells), after stimulation with pro-inflammatory cytokines or UV light, synthesize, and release aMSH. The effects of these peptides are mediated through spécifie melanocortin (MC) receptors that can be detected on immunocompetent and inflammatory cells as well as on keratinocytes, melanocytes, fibroblasts, and endothelial cells. In addition to its well known pigment-inducing capacity, aMSH is able to modulate keratinocyte proliferation and differentiation. Endothelial cell and fibroblast cytokiiie production and fibroblast collageiiase production are also regulated by aMSH. The imimmosup-pressive capacity of aMSH is mediated mainly through its effects on monocyte and macrophage functions. Accordingly, aMSH downrcgulates the production of pro-inflammatory cytokines and accessory molecules on antigen-presenting cells. The production of suppressor factors such as IL-10, however, is upregulated by aMSH. The in vivo relevance of these data is documented by the finding that systemic application of aMSH inhibits the induction and the elicitation of murine contact hyper-sensitivity and induces hapten-specific tolerance. These findings indicate that aMSH is part of the mediator network that regulates cutaneous inflammation and hyper-proliferative skin diseases. Copyright © 1997 by The Society for Investigative Dermatology, Inc.