Hong Seung P, Kim Min J, Jung Min-Young, Jeon Hyerin, Goo Jawoong, Ahn Sung K, Lee Seung H, Elias Peter M, Choi Eung H
Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
J Invest Dermatol. 2008 Dec;128(12):2880-7. doi: 10.1038/jid.2008.169. Epub 2008 Jun 26.
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.
虽然高剂量的紫外线B（UVB）对表皮渗透屏障有害，但亚红斑剂量的UVB可用于治疗特应性皮炎（AD），该病的特征是渗透屏障和抗菌功能存在缺陷。由于表皮渗透屏障和抗菌肽（AMP）表达是共同调节且相互依存的功能，我们推测亚红斑剂量的UVB暴露可与渗透屏障功能并行调节AMP表达。将无毛小鼠每天暴露于40 mJ/cm²的UVB（约为最小红斑剂量的1/2），持续1天或3天。最后一次暴露后24小时，评估表皮屏障功能，并采集皮肤标本进行蛋白质印迹、免疫组织化学以及针对小鼠β-防御素（mBD）-2、mBD3和组织蛋白酶相关抗菌肽（CRAMP）的定量逆转录聚合酶链反应。还对维生素D受体（VDR）、1α-羟化酶和关键表皮脂质合成酶的mRNA水平进行了定量。UVB暴露3天后，屏障恢复加速，表皮分化标志物（如内披蛋白和丝聚蛋白）的表达增加，同时mBD2、mBD3和CRAMP在mRNA和蛋白质水平的表达也增加。VDR、1α-羟化酶和主要的表皮脂质合成酶也上调。当在UVB暴露后立即应用1α,25-二羟基维生素D₃形成抑制剂酮康唑时，皮肤维生素D系统受到抑制，进而阻断了表皮脂质合成、AMP表达和渗透屏障稳态，这表明低剂量UVB的有益作用至少部分取决于皮肤维生素D系统的激活。我们的结果为低剂量UVB构成AD有效治疗方法的机制提供了新的见解。
