Biopositive Effects of Low-Dose UVB on Epidermis: Coordinate Upregulation of Antimicrobial Peptides and Permeability Barrier Reinforcement
Biopositive Effects of Low-Dose UVB on Epidermis: Coordinate Upregulation of Antimicrobial Peptides and Permeability Barrier Reinforcement
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DOI：
10.1038/jid.2008.169
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发表时间：
2008-12-01
影响因子：
6.5
通讯作者：
Choi, Eung H.
中科院分区：
文献类型：
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作者：
Hong, Seung P.;Kim, Min J.;Choi, Eung H.
针对大剂量中波紫外线(UVB)对皮肤通透性屏障的损害，亚低温剂量UVB被用于治疗特应性皮炎(AD)，其特点是透过性屏障和抗菌功能存在缺陷。由于表皮通透性屏障和抗菌肽(AMP)的表达是协同调节和相互依赖的功能，我们假设亚低温剂量的UVB照射可以与通透性屏障功能平行地调节AMP的表达。无毛小鼠每天暴露于40MJ cm(-2)UVB(约1/2最小红斑剂量)，持续1或3天。最后一次暴露24小时后，评估表皮屏障功能，取皮肤标本进行Western blotting、免疫组织化学和定量逆转录聚合酶链式反应(QRT-PCR)检测小鼠β-防御素(MBD)-2、MBD3和凯瑟琳相关抗菌肽(CARMP)。维生素D受体(VDR)、1α-羟基酶和关键的表皮脂合成酶的mRNA水平也被量化。UVB照射3d后，屏障恢复加快，表皮分化标志物(如总蛋白和微丝蛋白)的表达增加，同时Mbd2、MBD3和JRAMP在mRNA和蛋白水平上的表达也增加。VDR、1α-羟基酶和主要的表皮脂合成酶也上调。当1α，25二羟基维生素D-3形成的抑制剂酮康唑在UVB照射后立即应用时，皮肤维生素D系统被抑制，进而阻止表皮脂质合成、AMP表达和通透性屏障动态平衡，这表明低剂量UVB的有益作用至少部分依赖于皮肤维生素D系统的激活。我们的结果为低剂量UVB治疗AD的机制提供了新的见解。
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), 1 alpha-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 alpha-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1 alpha, 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.