Oral communication, GL7

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Alpha melanocyte stimulating hormone: a major component of the skin immune system with a therapeutic potential

Several components of the neuroendocrine system such as neuropeptides and hormones have been recognized to exert cytokine like effects via regulating innate as well as adaptive immunity. Among these neuromodulators α-melanocyte-stimulating hormone (αMSH) derived from the proopiomelanocortin was found to exhibit marked immunoregulating and anti-inflammatory activities. The effects of αMSH are mediated via direct effects on cells of the immune system as well as indirectly via affecting the function of resident non-immune cells. In order αMSH can exert these effects the expression of specific melanocortin receptors (MC-R) in particular MC-1R on both immunocompetent as well as non-immune cells is required. However, there is increasing evidence that αMSH can also penetrate independently of the expression of specific receptors in the cell and display its activity. αMSH affects several pathways implicated in regulation of inflammatory responses such as NF-κB activation, expression of adhesion molecules and chemokine receptors, production of proinflammatory cytokines and other mediators. Thus αMSH may modulate inflammatory cell proliferation, activity, and migration. Moreover, αMSH prevents the maturation of dendritic cells (DC) and thereby triggers the generation of a subset of regulatory T-cells. The anti-inflammatory and immunomodulatory effects of αMSH have been confirmed by means of animal models of inflammation such as irritant and allergic contact dermatitis, cutaneous vasculitis, psoriasis, inflammatory bowel disease as well as rheumatoid arthritis. Whereas the melanocyte stimulating activity of αMSH requires binding of the core tetrapeptide to MC-1R, there is accumulating evidence that the anti-inflammatory activities of αMSH can be attributed to its C-terminal tripeptide KPV and do not depend on the expression of a functional MC-1R. K(D)PT, a derivative of KPV corresponding to the amino acid 193-195 of IL-1β, is currently emerging as another tripeptide with potent anti-inflammatory effects. The anti-inflammatory potential together with the favourable physiochemical properties most likely will allow these agents to be developed for the treatment of inflammatory skin, joint, and bowel diseases.

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