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This version published online on August 4, 2005
Endocrinology, doi:10.1210/en.2005-0665
A more recent version of this article appeared on November 1, 2005
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Submitted on June 3, 2005
Accepted on July 26, 2005

Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of {alpha}-melanocyte-stimulating hormone in human dermal papilla cells

Markus Böhm*, Mareike Eickelmann, Zhuo Li, Stefan W. Schneider, Vinzenz Oji, Sven Diederichs, Gregory S. Barsh, Annika Vogt, Karola Stieler, Ulrike Blume-Peytavi, and Thomas A. Luger

Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, and Department of Medicine, Haematology and Oncology, University of Münster, Münster, Germany, Dept. of Pediatrics and Genetics, and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, Center for Applied Cutaneous Physiology, Department of Dermatology, University Hospital Charité, Berlin, Germany

* To whom correspondence should be addressed. E-mail: bohmm{at}uni-muenster.de.

Proopiomelanocortin (POMC)-derived peptides and their receptors have been identified in many peripheral organs including the skin where they exert a diversity of biological actions. We investigated the expression and potential role of the POMC system in human dermal papilla cells (DPC), a specialized cutaneous mesenchymal cell type regulating hair follicle activity. In culture, these cells expressed POMC and displayed immunoreactivity for ACTH, {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) and {beta}-endorphin. Among the prohormone convertases (PCs) tested, only PC2, its chaperone 7B2 and furin convertase but not PC1 and PACE4 were detected. Human DPC 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 (ASIP), a natural and highly selective MC-1R and MC-4R antagonist, was undetectable in human DPC. The MC-Rs detected in human DPC were functionally active as {alpha}-MSH increased intracellular cAMP and calcium. Preincubation of the cells with a synthetic peptide corresponding to the C-terminal domain of ASIP abrogated cAMP induction by {alpha}-MSH. Furthermore, {alpha}-MSH was capable of antagonizing the expression of intercellular adhesion molecule-1 induced by the proinflammatory cytokine interferon-{gamma}. Our data suggest a regulatory function of {alpha}-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.
Key words: Dermal papilla cells • hair follicle • melanocortin receptors • proopiomelanocortin • neuropeptides




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