BIOLOGICAL CLOCK AND CYTOKINE NETWORK

我们在2004年的研究中发现，在UVB照射后12小时，正常成纤维细胞中的β-1mRNA表达显著上调，而PER-1的表达显著下调。而Clock的表达则没有变化。在特应性皮炎患者的成纤维细胞中，与正常对照组相比，结果相反。这些结果表明，β-1和PER-1是分析UVB辐射后成纤维细胞生物钟表达模式的有用标记物，正常皮炎和特应性皮炎的表达模式与最初预期的不同。本研究旨在建立特应性皮炎患者昼夜颠倒后变态反应性炎症加重的动物模型，探讨特应性皮炎患者昼夜颠倒后过敏性炎症加重的机制。方法将9周龄雄性Balb/c小鼠随机分为A、B两组，每组再分为实验组和对照组。A组用UVB照射，每隔12h照射一次，连续6d。B组接受相同的UVB照射，但照射时间与A组相差12h。第6天，用0.2%DNFB在侧板上致敏。第1天，对耳廓皮肤进行激发试验。每隔12小时测量一次耳厚增加值。每只小鼠在激发试验后接受UVB照射24小时，A组接受相同照射，B组在黑暗条件下继续照射48-72小时，结果连续UVB照射组小鼠耳廓厚度较黑暗条件组增加，提示昼夜颠倒影响皮肤炎症。

We reported that significant upregulation of b mal-1 mRNA and downregulation of per-1 were observed at 12 hours after UVB irradiation in normal fibroblasts in the study performed in 2004. While expression of clock was unchanged. Reversed results were obtained in the fibroblasts derived from atopic dermatitis patients when compared to those from normal control. These results suggest that b mal-1 and per-1 are useful markers to analyze expression pattern of biological clock in UVB-irradiated fibroblasts and pattern is different between normal and atopic dermatitis as initially expected. This year we conducted to establish animal model to analyze the mechanism of exacerbation of allergic inflammation after reversal of day and night seen in atopic dermatitis patients which is the matter of discussion in the clinical fields.「Method」Nine week old male Balb/c mice were divided into two A and B groups and each group was subdivided into experimental and control groups. Group A were UVB irradiated for every 12 hours for 6 days. Group B were received same UVB irradiation but 12 hours shift of irradiation schedule from group A. On day 6, each mouse was sensitized with 0.2% DNFB on the flank ski. And on day 1, challenge test was performed on the pinna skin. Increase of ear thickness was measured every 12 hours. Each mouse received UVB irradiation for 24 hours after challenge test and group A received same irradiation and group B were kept under dark condition for next 48-72 hours.「Results」Increased ear thickness was observed in the group which received continuous UVB irradiation in contrast to the group which were kept under dark condition which suggests that reversal of day and night affect skin inflammation.