title: Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation.
abstract: Previous studies have shown that the protease-activated receptor 2 is involved in skin pigmentation through increased phagocytosis of melanosomes by keratinocytes. Ultraviolet irradiation is a potent stimulus for melanosome transfer. We show that protease-activated receptor 2 expression in human skin is upregulated by ultraviolet irradiation. Subjects with skin type I, II, or III were exposed to two or three minimal erythema doses of irradiation from a solar simulator. Biopsies were taken from nonexposed and irradiated skin 24 and 96 h after irradiation and protease-activated receptor 2 expression was detected using immunohistochemical staining. In nonirradiated skin, protease-activated receptor 2 expression was confined to keratinocytes in the lower one-third of the epidermis. After ultraviolet irradiation protease-activated receptor 2 expression was observed in keratinocytes in the upper two-thirds of the epidermis or the entire epidermis at both time points studied. Subjects with skin type I showed delayed upregulation of protease-activated receptor 2 expression, however, compared with subjects with skin types II and III. Irradiated cultured human keratinocytes showed upregulation in protease-activated receptor 2 expression as determined by immunofluorescence microscopy and Western blotting. Cell culture supernatants from irradiated keratinocytes also exhibited a dose-dependent increase in protease-activated receptor-2 cleavage activity. These results suggest an important role for protease-activated receptor-2 in pigmentation in vivo. Differences in protease-activated receptor 2 regulation in type I skin compared with skin types II and III suggest a potential mechanism for differences in tanning in subjects with different skin types.
authors.affiliation: Department of Dermatology, University of Rochester Medical Center, School of Medicine, Rochester, New York 14642, USA. Glynis_Scott@urmc.edu
authors.forename: G
authors.initials: G
authors.lastname: Scott
authors.forename: A
authors.initials: A
authors.lastname: Deng
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Burford
authors.forename: M
authors.initials: M
authors.lastname: Seiberg
authors.forename: R
authors.initials: R
authors.lastname: Han
authors.forename: L
authors.initials: L
authors.lastname: Babiarz
authors.forename: W
authors.initials: W
authors.lastname: Grizzle
authors.forename: W
authors.initials: W
authors.lastname: Bell
authors.forename: A
authors.initials: A
authors.lastname: Pentland
mesh_terms: D000328:Adult; D000368:Aged; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000201:enzymology; D008297:Male; D020460:Melanosomes / Q000378:metabolism*; D008875:Middle Aged; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D012880:Skin Pigmentation / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D010450:Endopeptidases