Evidence for Expression of Melanocortin-1 Receptor in Human Sebocytes In Vitro and In Situ

Abstract

Many lines of evidence indicate that the activity of sebaceous glands can be modulated by neuropeptides. Direct evidence in man, however, is still missing. We show that SZ95 sebocytes, an immortalized human sebaceous gland cell line, express receptors for alpha-melanocyte-stimulating hormone. Reverse transcription polymerase chain reaction with primers against the five melanocortin receptors and immunofluorescence studies using an antibody directed against a peptide corresponding to the amino acids 2-18 of the human melanocortin-1 receptor disclosed specific transcripts and immunoreactivity for melanocortin-1 receptor in these cells. Melanocortin-1 receptor expression was confirmed in sebocytes of normal human skin by immunohistochemistry. In contrast, no immunostaining for the melanocortin-5 receptor could be detected in sebocytes in situ, in accordance with the lack of specific transcripts for this melanocortin receptor in SZ95 sebocytes. As cytokines play an important role in the recruitment of inflammatory cells in acne and related disorders and alpha-melanocyte-stimulating hormone exerts immunomodulatory effects in many other cell types, we investigated the effect of alpha-melanocyte-stimulating hormone on interleukin-8 secretion by SZ95 sebocytes. Treatment with interleukin-1beta resulted in a marked increase in interleukin-8 release that was partially blocked by coincubation with alpha-melanocyte-stimulating hormone in a dose-dependent manner. Taken together, we show here that the melanocortin-1 receptor is expressed in vitro and in situ in human sebocytes. By modulating interleukin-8 secretion, alpha-melanocyte-stimulating hormone may act as a modulator of inflammatory responses in the pilosebaceous unit.

Corticotropin-releasing hormone: An autocrine hormone that promotes lipogenesis in human sebocytes

“…It also seems to be involved in responses to stress, expressing receptors for ␣-melanocyte-stimulating hormone (␣-MSH; ref. 21), ␤-endorphin, † † vasoactive intestinal polypeptide, neuropeptide Y, and calcitonin gene-related peptide. ‡ ‡ ␣-MSH and calcitonin generelated peptide down-regulate the enhanced IL-8 synthesis in IL-1␤-challenged human sebocytes, but are not produced in human sebocytes themselves (21).…”

“…21), ␤-endorphin, † † vasoactive intestinal polypeptide, neuropeptide Y, and calcitonin gene-related peptide. ‡ ‡ ␣-MSH and calcitonin generelated peptide down-regulate the enhanced IL-8 synthesis in IL-1␤-challenged human sebocytes, but are not produced in human sebocytes themselves (21). ‡ ‡ ␤-Endorphin is also a paracrine neuropeptide for human sebocytes, which suppresses their proliferation induced by epidermal growth factor in Ca 2ϩ -rich medium.…”

An update on the role of the sebaceous gland in the pathogenesis of acne

“…The expression of MC-5R is weaker than that of MC1-R but it has been shown to be a marker of human sebocyte differentiation, since it is expressed in differentiated, lipid-containing sebocytes only. 63,64 In acne-involved skin, sebocytes and keratinocytes of the ductus seboglandularis showed very intense MC-1R expression in contrast to less intense scattered immunoreactivity in normal skin samples suggesting that this receptor is involved in the initiation of acne. 65 MC-1R expression has been shown to be upregulated by proinflammatory signals.…”

“…66,67 As proinflammatory cytokines are upregulated in acne lesions, 68 sebocytes may respond to these signals with increased MC-1R expression, thereby generating a negative feedback mechanism for α-MSH which exerts direct anti-inflammatory actions, i.e., inhibition of IL-1-mediated IL-8 secretion. 64,65 Cannabinoid receptors (CR), which mediate the psychopharmacological action of marijuana have been not only localised in the central and peripheral nervous system but also in human skin. CR1 and 2 are expressed in human sebaceous glands, 69 whereas the CB2 and other prototypic endocannabinoids are present in SZ95 sebocytes and may induce in a dose-dependent manner lipid production and cell death.…”

Beyond acne: Current aspects of sebaceous gland biology and function

“…As proinflammatory cytokines are up-regulated in acne lesions, sebocytes may respond to these signals with increased MC-1R expression, thereby generating a negative feedback mechanism for α-MSH which exerts direct anti-inflammatory actions, i.e. inhibition of IL-1-mediated IL-8 secretion [105,106].…”