Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal papilla cells.
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, alphaMSH, and beta-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 alphaMSH 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 alphaMSH. Furthermore, alphaMSH 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 alphaMSH 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.
Böhm
Markus
M
Department of Dermatology, University of Münster, Von Esmarch-Str. 58, D-48149 Münster, Germany. bohmm@uni-muenster.de
Eickelmann
Mareike
M
Li
Zhuo
Z
Schneider
Stefan W
SW
Oji
Vinzenz
V
Diederichs
Sven
S
Barsh
Gregory S
GS
Vogt
Annika
A
Stieler
Karola
K
Blume-Peytavi
Ulrike
U
Luger
Thomas A
TA
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D054366:Agouti Signaling Protein; D002478:Cells, Cultured; D020405:Dermis / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D045683:Furin / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051859:Neuroendocrine Secretory Protein 7B2 / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D000521:alpha-MSH / Q000502:physiology*; D001615:beta-Endorphin / Q000378:metabolism
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; C470072:MC4R protein, human; D008565:Membrane Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4; C497678:SCG5 protein, human; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; C468731:FURIN protein, human; D045683:Furin; D045706:Proprotein Convertase 2