Expression of melanocortin receptors on cutaneous fibroblastic cells – collagen and beyond

Abstract

Melanocortin receptors (MC‐Rs) mediate the biological actions of the members of melanocortin family, e.g. of α‐melanocyte‐stimulating hormone (α‐MSH) and adrenocorticotropin. We recently reported that human dermal fibroblasts derived from newborn foreskin express MC‐1R. In these cells and in a newborn mouse model of cutaneous fibrosis, α‐MSH suppressed collagen synthesis induced by the profibrotic cytokine transforming growth factor‐β1(Böhm et al., J. Biol. Chem. 2004). Here, we show that MC‐1R expression is maintained in various fibroblastic skin cell types established from adult human skin. In vitro, expression of MC‐1R at the RNA level was detected by RT‐PCR analysis in dermal fibroblasts, dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle, as well as in HT1080 fibrosarcoma cells. In all of the latter cell types except in HT1080 cells, MC‐1R immunoreactivity could be visualized on the cell surface as demonstrated by immunofluorescence studies using an antibody against the amino acids 2–18 of the N‐terminal domain of human MC‐1R. In situ, MC‐1R expression was detectable in interfollicular dermal fibroblasts only by immune electron microscopy. In contrast, MC‐1R expression was detectable in dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle by conventional immunohistochemistry. To further assess the relevance of MC‐1R being expressed in fibroblastic cells of the skin we treated human dermal fibroblasts in vitro with the proinflammatory cytokine interferon‐γ(IFN‐γ). α‐MSH significantly suppressed the upregulating effect of this cytokine on the expression of intercellular adhesion molecule‐1 (ICAM‐1), an adhesion molecule crucially involved in recruitment of activated leukocytes into the hair follicle. In summary, our findings form a basis upon which MC‐1R expression can be investigated in inflammatory disorders affecting the connective tissue compartment of the skin. Moreover, our preliminary data on the modulation of IFN‐γ‐driven upregulation of ICAM‐1 by α‐MSH suggest additional functions of melancortins in fibroblasts beyond collagen synthesis.