title: Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement.
abstract: Whereas high-dose ultraviolet B (UVB) is detrimental to the epidermal permeability barrier, suberythemal doses of UVB are used to treat atopic dermatitis (AD), which is characterized by defective permeability barrier and antimicrobial function. As epidermal permeability barrier and antimicrobial peptide (AMP) expression are coregulated and interdependent functions, we hypothesized that suberythemal doses of UVB exposure could regulate AMP expression in parallel with permeability barrier function. Hairless mice were exposed to 40 mJ cm(-2) UVB (about 1/2 minimal erythema dose) daily for 1 or 3 days. Twenty-four hours after the last exposure, epidermal barrier function was assessed and skin specimens were taken for western blotting, immunohistochemistry, and quantitative reverse transcription-PCR for mouse beta-defensin (mBD)-2, mBD3 and cathelin-related antimicrobial peptide (CRAMP). mRNA levels of the vitamin D receptor (VDR), 1alpha-hydroxylase and key epidermal lipid synthetic enzymes were also quantified. After 3 days of UVB exposure, acceleration of barrier recovery and augmentation in expression of epidermal differentiation markers (for example, involucrin and filaggrin) occurred in parallel with increased mBD2, mBD3, and CRAMP expression at both the mRNA and protein level. VDR, 1alpha-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1alpha, 25 dihydroxyvitamin D(3) formation, ketoconazole, was applied immediately after UVB exposure, the cutaneous vitamin D system was inhibited, which in turn blocked epidermal lipid synthesis, AMP expression, and permeability barrier homeostasis, suggesting that the beneficial effect of low-dose UVB depends, at least in part, on activation of the cutaneous vitamin D system. Our results provide new insights into the mechanisms whereby low-dose UVB comprises effective therapy for AD.
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Seung P
authors.initials: SP
authors.lastname: Hong
authors.forename: Min J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Jung
authors.forename: Hyerin
authors.initials: H
authors.lastname: Jeon
authors.forename: Jawoong
authors.initials: J
authors.lastname: Goo
authors.forename: Sung K
authors.initials: SK
authors.lastname: Ahn
authors.forename: Seung H
authors.initials: SH
authors.lastname: Lee
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Eung H
authors.initials: EH
authors.lastname: Choi
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D054804:Cathelicidins; D002454:Cell Differentiation; D002762:Cholecalciferol / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000528:radiation effects*; D005260:Female; D007150:Immunohistochemistry; D007654:Ketoconazole / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008812:Mice, Hairless; D008954:Models, Biological; D010539:Permeability; D018167:Receptors, Calcitriol / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008055:Lipids; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D007654:Ketoconazole