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

(1)长期外用糖皮质激素对接触性增敏反应的诱导我们进一步分析了长期外用类固醇(隔天9次)对接触性敏感性反应增强性的调节机制。在这个系统中，我们发现区域淋巴结中的Gamma Delta阳性细胞数量显著增加，这些细胞可能参与了皮肤反应的增强。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，提示糖皮质激素可增强各种类型的皮肤炎症。(2)长期局部应用糖皮质激素后皮肤中的细胞因子谱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超级水剂下调了糖皮质激素治疗小鼠的皮肤增强反应，提示糖皮质激素可能下调角质形成细胞产生抗炎分子或上调促炎症细胞因子的产生。为了阐明这一点，如果局部注射IL10或IL1ra明显抑制糖皮质激素诱导的皮肤反应，聚合酶链式反应分析和免疫组织化学分析显示，在糖皮质激素诱导的皮肤反应的皮损角质形成细胞中，IL10和IL1α的表达下调。(3)糖皮质激素诱导PROLNFLAMMATY细胞TOKINES上调的调节机制。我们发现，氢化可的松明显促进DNBS和TNBS诱导的前炎性角质形成细胞(IL1和1L6)的产生，而抑制IL10的产生。这些结果表明ILLO在皮肤炎症中起重要作用。IL-10在核因子-K-B活化中的作用有待进一步研究。

(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.