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Detection of Functionally Active Melanocortin Receptors and Evidence for an Immunoregulatory Activity of -Melanocyte-Stimulating Hormone in Human Dermal Papilla Cells

Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin (M.B., M.E., Z.L., S.W.S., V.O., T.A.L.) and Department of Medicine, Hematology, and Oncology (S.D.), University of Münster, D-48149 Münster, Germany; Department of Pediatrics and Genetics and the Howard Hughes Medical Institute (G.S.B.), Stanford University School of Medicine, Stanford, California 94305; and Department of Dermatology (A.V., K.S., U.B.-P.), Center for Applied Cutaneous Physiology, University Hospital Charité, D-10117 Berlin, Germany

Address all correspondence and requests for reprints to: Markus Böhm, M.D., Department of Dermatology, University of Münster, Von Esmarch-Str. 58, D-48149 Münster, Germany. E-mail: bohmm{at}uni-muenster.de.

Proopiomelanocortin (POMC)-derived peptides and their receptors have been identified in many peripheral organs including the skin in which they exert a diversity of biological actions. We investigated the expression and potential role of the POMC system in human dermal papilla cells (DPCs), a specialized cutaneous mesenchymal cell type regulating hair follicle activity. In culture, these cells expressed POMC and displayed immunoreactivity for ACTH, MSH, and ß-endorphin. Among the prohormone convertases (PCs) tested, only PC2, its chaperone 7B2, and furin convertase but not PC1 and paired basic amino acid cleaving enzyme 4 gene were detected. Human DPCs in vitro expressed both the melanocortin-1 receptor (MC-1R) and MC-4R, and immunoreactivity for these receptors was also present in cells of the human dermal papilla in situ. In contrast to the dermal papilla of agouti mice, agouti signaling protein, a natural and highly selective MC-1R and MC-4R antagonist, was undetectable in human DPCs. The MC-Rs detected in human DPCs were functionally active because MSH increased intracellular cAMP and calcium. Preincubation of the cells with a synthetic peptide corresponding to the C-terminal domain of agouti signaling protein abrogated cAMP induction by MSH. Furthermore, MSH was capable of antagonizing the expression of intercellular adhesion molecule-1 induced by the proinflammatory cytokine interferon-. Our data suggest a regulatory function of MSH within the dermal papilla whose disruption may lead to deregulation of immune and inflammatory responses of the hair follicle, thereby possibly contributing to the development of inflammatory forms of alopecia.

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