The role of alpha-MSH as a modulator of cutaneous inflammation.
Among various neuropeptides such as substance P, calcitonin gene-related peptide and others, alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC-1R), which is specific for alpha-MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFN-gamma, TNF-alpha and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NF kappa B is downregulated by alpha-MSH. In a mouse model i.v. or topical application of alpha-MSH was found to inhibit the induction phase as well as the effector phase of contact hypersensitivity (CHS) reactions and to induce hapten-specific tolerance. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Münster, Germany. luger@uni-muenster.de
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D000818:Animals; D006801:Humans; D007249:Inflammation; D015213:Neuroimmunomodulation; D018043:Receptors, Corticotropin / Q000276:immunology; D044101:Receptors, Melanocortin; D012871:Skin Diseases / Q000276:immunology*; D000521:alpha-MSH / Q000276:immunology*
D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH