title: Fibroblasts play a regulatory role in the control of pigmentation in reconstructed human skin from skin types I and II.
abstract: Human melanocytes in monolayer culture are extremely dependent on a wide range of soluble signals for their proliferation and melanogenesis. The advent of three-dimensional models of reconstructed skin allows one to ask questions of how these cells are regulated within a setting which more closely approximates normal skin. The purpose of this study was to investigate to what extent melanocytes within a reconstructed skin model are sensitive to regulation by dermal fibroblasts, basement membrane (BM) proteins and the addition of alpha-melanocyte-stimulating hormone (alpha-MSH). Sterilized acellular de-epidermized dermis (prepared to retain BM proteins or deliberately denuded of BM by enzymatic treatment) from skin type I or II was reconstituted with fibroblasts, melanocytes and keratinocytes. In all but one case (9/10), cell donors were skin type I or II. The presence of BM antigens was found to be necessary for positional orientation of the melanocytes; in the absence of BM, melanocytes moved into the upper keratinocyte layer pigmenting spontaneously. Addition of fibroblasts suppressed the extent of spontaneous pigmentation of melanocytes within this model. Neither alpha-MSH nor cholera toxin induced pigmentation in this model despite the fact that melanocytes clearly had the ability to synthesize pigment.
authors.affiliation: University Section of Medicine, Division of Clinical Sciences, Northern General Hospital, Sheffield, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hedley
authors.forename: Christopher
authors.initials: C
authors.lastname: Layton
authors.forename: Martin
authors.initials: M
authors.lastname: Heaton
authors.forename: Kaushik H
authors.initials: KH
authors.lastname: Chakrabarty
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Dawson
authors.forename: David J
authors.initials: DJ
authors.lastname: Gawkrodger
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
mesh_terms: D000328:Adult; D001485:Basement Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology*; D020460:Melanosomes / Q000378:metabolism; D012867:Skin / Q000166:cytology; D012880:Skin Pigmentation / Q000502:physiology*; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D000521:alpha-MSH; D002772:Cholera Toxin