1. ¹Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
2. ²Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea
3. ³Department of Dermatology, University of California San Francisco and Dermatology Service, Veteran's Administration Medical Center, San Francisco, California, USA
4. ⁴Yonsei Institute of Lifelong Health, Wonju, Korea

Correspondence: Dr Eung Ho Choi, Department of Dermatology, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju 220-701, Korea. E-mail: choieh@yonsei.ac.kr

Received 16 October 2007; Revised 25 April 2008; Accepted 25 April 2008; Published online 26 June 2008.

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 -defensin (mBD)-2, mBD3 and cathelin-related antimicrobial peptide (CRAMP). mRNA levels of the vitamin D receptor (VDR), 1-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, 1-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1, 25 dihydroxyvitamin D₃ 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.