title: The aryl hydrocarbon receptor mediates UVB radiation-induced skin tanning.
abstract: Melanogenesis is the vital response to protect skin cells against UVB-induced DNA damage. Melanin is produced by melanocytes, which transfer it to surrounding keratinocytes. Recently, we have shown that the aryl hydrocarbon receptor (AhR) is part of the UVB-stress response in epidermal keratinocytes. UVB triggers AhR signaling by generating the AhR ligand 6-formylindolo(3,2-b)carbazole from tryptophan. We show here that normal murine melanocytes express functional AhR. Using standard UVB tanning protocols, AhR-deficient mice were shown to tan significantly weaker than wild-type mice; in these mice, tyrosinase activity in the epidermis was lower as well. Tanning responses and tyrosinase activity, however, were normal in keratinocyte-specific conditional AhR knockout mice, indicating that release of melanogenic keratinocyte factors is unaffected by the UVB-AhR signaling pathway and that the diminished tanning response in AhR(-/-) mice is confined to the level of melanocytes. Accordingly, the number of dihydroxyphenylalanin-positive melanocytes increased significantly less on UVB irradiation in AhR(-/-) mice than in wild-type mice. This difference in melanocyte number was associated with a significantly reduced expression of stem cell factor-1 and c-kit in melanocytes of AhR(-/-) mice. Thus, the environmental signal sensor AhR links solar UVB radiation to skin pigmentation.
authors.affiliation: Leibniz Institute for Environmental Medical Research (IUF), Düsseldorf, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Jux
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kadow
authors.forename: Sandra
authors.initials: S
authors.lastname: Luecke
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Jean
authors.initials: J
authors.lastname: Krutmann
authors.forename: Charlotte
authors.initials: C
authors.lastname: Esser
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology / Q000528:radiation effects; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D012880:Skin Pigmentation / Q000502:physiology* / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D018336:Receptors, Aryl Hydrocarbon