Atarashi Kenji, Kabashima Kenji, Akiyama Katsuhiko, Tokura Yoshiki
Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
J Dermatol Sci. 2007 Aug;47(2):151-9. doi: 10.1016/j.jdermsci.2007.04.001. Epub 2007 May 23.
Ketoprofen (KP) clinically evokes the allergic type of photocontact dermatitis when applied to the skin and irradiated with ultraviolet A (UVA). We have established a murine model of photocontact dermatitis to KP, which is a T cell-mediated delayed type hypersensitivity.
To further explore the mechanism underlying this sensitivity, we investigated whether KP plus UVA activates the antigen-presenting ability of Langerhans cells (LCs).
We analyzed the expression of surface molecules on LCs in the murine epidermis treated with KP plus UVA by immunohistochemistry and flow cytometry. Changes in the cytokine expression of epidermal cells from KP-phototreated skin were also examined by real-time PCR.
LCs became larger after treatment with KP plus UVA. The number of LCs was significantly decreased 2-3 days after KP phototreatment and recovered on day 5. A flow cytometric analysis revealed that KP plus UVA increased the percentage of LCs that highly expressed MHC class II, CD86, CD80, CD54 and CD40, whereas neither KP nor UVA alone enhanced the expression. KP phototreatment augmented the expression of I-A and CD86 on LCs in KP and UVA dose-dependent manners. A real-time PCR analysis of KP-phototreated skin showed that the expression of mRNA for IL-1alpha and GM-CSF was immediately increased after treatment.
A photosensitizing regimen of KP plus UVA activates LCs at least partly by stimulating keratinocytes to produce cytokines. Two strains of mice (BALB/c and AKR) differ in responsiveness to KP and the difference is not related to the activation of keratinocytes.
酮洛芬（KP）应用于皮肤并接受紫外线A（UVA）照射时，临床上会引发过敏性光接触性皮炎。我们已经建立了一种针对KP的光接触性皮炎小鼠模型，这是一种T细胞介导的迟发型超敏反应。
为了进一步探究这种敏感性的潜在机制，我们研究了KP加UVA是否会激活朗格汉斯细胞（LCs）的抗原呈递能力。
我们通过免疫组织化学和流式细胞术分析了用KP加UVA处理的小鼠表皮中LCs表面分子的表达。还用实时PCR检测了经KP光处理皮肤的表皮细胞细胞因子表达的变化。
用KP加UVA处理后，LCs变大。KP光处理后2 - 3天，LCs数量显著减少，并在第5天恢复。流式细胞术分析显示，KP加UVA增加了高表达MHC II类、CD86、CD80、CD54和CD40的LCs百分比，而单独的KP或UVA均未增强这种表达。KP光处理以KP和UVA剂量依赖性方式增强了LCs上I - A和CD86的表达。对经KP光处理皮肤的实时PCR分析表明，处理后IL - 1α和GM - CSF的mRNA表达立即增加。
KP加UVA的光敏方案至少部分通过刺激角质形成细胞产生细胞因子来激活LCs。两株小鼠（BALB/c和AKR）对KP的反应性不同，且这种差异与角质形成细胞的激活无关。
