Fibroblasts Play a Regulatory Role in the Control of Pigmentation in Reconstructed Human Skin from Skin Types I and II

Hedley, Susan J.; Layton, Christopher; Heaton, Martin; Chakrabarty, K; Dawson, Rebecca; Gawkrodger, David J.; Neil, S. Mac

doi:10.1034/j.1600-0749.2002.00067.x

Cited by 75 publications

(58 citation statements)

References 49 publications

(88 reference statements)

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“…Although cultured mouse melanocytes and melanoma cells reliably pigment to a-MSH addition (Eberle, 1988), human melanocytes have little or no response (Friedmann et al, 1990;De Luca et al, 1993;Hedley et al, 1998a). Responses relate to skin type (Hunt et al, 1994) with melanocytes from type 1 and type 2 skin donors rarely pigmenting to a-MSH in vitro, whether in 2-D (Hedley et al, 1998a) or 3-D culture (Hedley et al, 2002).…”

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confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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a-Melanocyte stimulating hormone (a-MSH) is known to have pleiotrophic functions including pigmentary, anti-inflammatory, antipyretic and immunoregulatory roles in the mammalian body. It is also reported to influence melanoma invasion with levels of a-, b-and g-MSH correlated clinically with malignant melanoma development, but other studies suggest a-MSH acts to retard invasion. In the present study, we investigated the action of a-MSH on three human melanoma cell lines (HBL, A375-SM and C8161) differing in metastatic potential. a-melanocyte-simulating hormone reduced invasion through fibronectin and also through a human reconstructed skin composite model for the HBL line, and inhibited proinflammatory cytokine-stimulated activation of the NF-kB transcription factor. However, A375-SM and C8161 cells did not respond to a-MSH. Immunofluorescent microscopy and Western blotting identified melanocortin-1 receptor (MC-1R) expression for all three lines and MC-2R on HBL and A375-SM lines. Receptor binding identified a similar affinity for a-MSH for all three lines with the highest number of binding sites on HBL cells. Only the HBL melanoma line demonstrated a detectable cyclic adenosine monophosphate (cAMP) response to a-MSH, although all three lines responded to acute a-MSH addition ( þ (À)-N 6 -(2-phenylisopropyl)-adenosine (PIA)) with an elevation in intracellular calcium. The nonresponsive lines displayed MC-1R polymorphisms (C8161, Arg (wt) 151/Cys 151; A375-SM, homozygous Cys 151), whereas the HBL line was wild type. Stable transfection of the C8161 line with wild-type MC-1R produced cells whose invasion was significantly inhibited by a-MSH. From this data, we conclude that a-MSH can reduce melanoma cell invasion and protect cells against proinflammatory cytokine attack in cells with the wild-type receptor (HBL).

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confidence: 99%

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

et al. 2003

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“…It was recently reported that the hypopigmentation of palmoplantar skin (on the palms and soles) compared to nonpalmoplantar (trunk) skin in humans is regulated by dermal fibroblasts in those areas, specifically via a secreted factor (Dickkopf-related protein 1; DKK1) that regulates Wnt signaling (Yamaguchi et al, 2004;Yamaguchi et al, 2007b;Yamaguchi et al, 2008). Furthermore, several other studies have shown the influence of dermal fibroblasts on human epidermal pigmentation (Cario-Andre et al, 2006;Hedley et al, 2002). Therefore, we hypothesized that fibroblasts in the dermis of trunk skin play important functions in regulating the constitutive color of different phototypes of skin and their responses to the environment, particularly via the factors they secrete.…”

Section: Introductionmentioning

confidence: 99%

The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin

Choi

Wolber

Gerwat

et al. 2010

Journal of Cell Science

101

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SummaryInteractions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. In this study, we tested the hypothesis that dermal fibroblasts regulate the constitutive skin color of individuals ranging from very light to very dark. We used microarray analysis to compare gene expression patterns in fibroblasts derived from lighter skin types compared to darker skin types, with a focus on secreted proteins. We identified a number of genes that differ dramatically in expression and, among the expressed proteins, neuregulin-1, which is secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting that it is one of the major factors determining human skin color.

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“…Earlier studies have shown that the melanin production in melanocytes is influenced by keratinocytes and fibroblasts. [23,24] Primary human melanocytes and keratinocytes have some drawbacks such as the limited proliferate capacity and the donor variability. Thus the use of immortalized cell lines would be more suitable for investigating the effects of pigmentation regulators.…”

Section: Discussionmentioning

confidence: 99%

Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte-keratinocyte co-culture and monolayer culture of melanocytes

Liu

Chu

Pan

2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte -keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds.

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Fibroblasts Play a Regulatory Role in the Control of Pigmentation in Reconstructed Human Skin from Skin Types I and II

Cited by 75 publications

References 49 publications

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

Anti-inflammatory and anti-invasive effects of α-melanocyte-stimulating hormone in human melanoma cells

The fibroblast-derived paracrine factor neuregulin-1 has a novel role in regulating the constitutive color and melanocyte function in human skin

Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte-keratinocyte co-culture and monolayer culture of melanocytes

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