IDENTIFICATION AND REGULATORY MECHANISMS OF INTRINSIC ANTI-INFLAMMATORY MOLECULES IN THE SKIN

(1)长期外用糖皮质激素诱导接触敏感反应增强我们进一步分析了长期外用类固醇（隔天使用9次）增强接触敏感反应的调控机制。在该系统中，我们发现区域淋巴结的γ δ阳性细胞数量显著增加，这些细胞可能有助于增强皮肤反应。此外，长期局部应用糖皮质激素可增强IgE介导的皮肤过敏反应，这表明糖皮质激素可增强各种类型的皮肤炎症。(2)长期外用糖皮质激素对皮肤细胞因子的影响我们发现，局部注射从冷冻和解冻的角质形成细胞中获得的上剂可下调糖皮质激素处理小鼠的增强皮肤反应，这表明糖皮质激素可能下调角质形成细胞产生的抗炎分子或上调炎症原细胞因子的产生。为了阐明这些观点，局部注射il - 10或il - 1ra可以明显引起不调节的糖皮质激素诱导的增广皮肤反应，PCR分析和免疫组织化学分析显示糖皮质激素诱导的增广皮肤反应病灶角质形成细胞中il - 10下调，il - 1 α上调。(3)糖皮质激素诱导促炎细胞因子上调的调控机制。我们发现氢化可的松明显增加了半抗原（DNBS和TNBS）诱导的促炎因子（il1a和1L6）的产生和NF κ B在培养的人角质形成细胞中的表达，同时下调了IL10的产生。这些结果表明，iLlO在皮肤炎症中起重要作用。需要进一步的研究来阐明IL10在NF - K - B活化中的作用。

(1) INDUCTION OF AUGMENTED CONTACT SENSITIVITY REACTION BY LONG TERM APPLICATION OF TOPICAL GLUCOCORTICOIDWe further analyzed the regulatory mechanisms of augmentation of contact sensitivity reaction by long-term application of topical steroid (9 times application on alternate days). In this system, we found that number of gamma delta' positive cells significantly increased in the regional lymph node and these cells might contribute on augmented skin reaction. In addition, long term topical application of glucocorticoid augmented IgE mediated anaphylactic reaction of the skin which suggests that glucocorticoid enhance various types of cutaneous inflammation.(2) CYTOKNE PROFILES IN THE SKIN AFTER LONG TERM APPLICATION OF TOPICAL GLUCOCORTICOIDWe found that local injection of supernavant obtained from freeze and thawed-kerarinocytes down regulated augmented skin reaction of glucocorticoid treated mouse which suggests that glucocotticoid might down regulate the production of anti-inflammatory molecules by keratinocytes or up regulate the production of proinfiammatoty cytokines. To clarify these points, local injections if IL10 or IL1ra clearly do unregulated glucocorticoid induced-augmented skin reaction, PCR ana1ysis and immunohistochemical analysis revealed down regulation of IL10 and upreguadon of IL1 alpha in the lesional keratinocytes of glucocorticoid induced augmented skin reaction.(3) REGULATORY MECHANISMS OF GLUCOCORTICOID INDUCED UPREGULATION OF PROLNFLAMMATORY CYTOKINES.We found that hydrocortison clearly augmented hapten(DNBS and TNBS)-induced proinflammatory cvtokine (IL1 a and 1L6) productions and NF kappa B expression by cultured human keratinocytes while down regulated IL10 production. These results indicate that iLlO plays important role in cutaneous inflammation. Further study is needed to clarify the role of IL10 in NF K B activation.