细菌超抗原SEB抑制小鼠角质形成细胞糖皮质激素受体核转移的实验研究

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目的探讨金黄色葡萄球菌肠毒素B(SEB)对小鼠角质形成细胞糖皮质激素受体GRα核转移的影响。方法 1%二硝基氯苯重复刺激Balb/c小鼠背部皮肤构建变应性接触性皮炎动物模型,分别用SEB、地塞米松、SEB+地塞米松处理该模型鼠背部局部皮肤,处理48 h后HE染色计数真皮内炎性细胞数量,免疫荧光和Western blot法观察GRα在各组角质形成细胞的胞浆和核浆分布,ELISA法观察IL-2、4、13和TNF-α等炎症因子在各组的表达变化。结果 SEB处理后真皮内炎性细胞显著增加。地塞米松可显著减少炎性细胞数目,而SEB可部分拮抗地塞米松的抗炎作用;激光共聚焦显示正常角质形成细胞GRα主要存在于细胞浆,少量存在于胞核。地塞米松可显著增加GRα核/浆阳性比值,而SEB可显著减弱地塞米松诱导的GRα核/浆阳性比值;Western blot检测也显示地塞米松处理后GRα蛋白入核量显著增多,而SEB可显著抑制地塞米松诱导的GRα蛋白入核量,并增加GRα蛋白胞浆滞留;与正常组相比,皮炎组IL-2、4、13和TNF-α表达均显著升高,地塞米松可显著抑制各炎症因子增多,而SEB可显著拮抗地塞米松对炎性因子的抑制作用。结论 SEB在局部皮炎诱导的激素减敏与其抑制角质形成细胞GRα核转移障碍有关。 Objective To investigate the effect of staphylococcal enterotoxin B (SEB) on the nuclear translocation of glucocorticoid receptor GRα in mouse keratinocytes. Methods The animal model of allergic contact dermatitis was established by repetitive stimulation of 1% dinitrochlorobenzene on the skin of Balb / c mice. The skin of the back of the model mice was treated with SEB, dexamethasone and SEB + dexamethasone for 48 h The number of inflammatory cells in the dermis was counted by HE staining. The distribution of GRα in the cytoplasm and nucleus of keratinocytes in each group was observed by immunofluorescence and Western blot. The inflammatory cytokines such as IL-2, 4, 13 and TNF-α The expression changes in each group. Results SEB treated dermal intradermal inflammatory cells increased significantly. Dexamethasone can significantly reduce the number of inflammatory cells, while SEB can partially antagonize the anti-inflammatory effect of dexamethasone; confocal laser scanning confocal microscope showed that the normal keratinocytes GRα mainly exists in the cytoplasm, a small number in the nucleus. Dexamethasone can significantly increase the ratio of GRα nuclear / plasma, while SEB can significantly reduce dexamethasone-induced GRα nuclear / plasma positive ratio; Western blot also showed that dexamethasone treated GRα protein nuclear significantly increased, while SEB Dexamethasone can significantly inhibit the GRα-induced nuclear into the nucleus and GRα protein cytoplasmic retention; compared with the normal group, dermatitis group IL-2, 4, 13 and TNF-α expression were significantly increased, dexamethasone Can significantly inhibit the increase of inflammatory cytokines, and SEB can significantly antagonize the dexamethasone on the inhibition of inflammatory cytokines. Conclusions The desensitization of SEB induced by local dermatitis is related to the inhibition of GRα nuclear transfer disorder in keratinocytes.
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