吡格列酮对脂多糖刺激的星形胶质细胞白介素-1β的抑制作用及机制

摘要

Aim To investigate whether pioglitazone could protect cortical astrocytes from LPS-induced expressions of IL-1 β and the mechanisms responsible for this protective effect. Methods Cultured astrocytes were treated with LPS (10 mg · L-1 ) for 24 h, in the absence or presence of pioglitazone ( 0. 1, 1.0 and 10. 0 μmol· L-1 ) or the specific inhibitor of JNK SP600125 ( 10. 0 μmol · L-1 ), and harvested. IL-1β was analysed by ELISA and immunofluorescent technology. Western blot was performed to observe the level of p-JNK and p-c-Jun in cultured astrocytes. Results LPS significantly induced increase in phospho-JNKl, phospho-c-Jun protein expression without affecting total protein levels and increase the expression and production of IL-1 β in cultured astrocytes in rats. Pioglitazone inhibited LPS-induced increase in expression of IL-1 β, and p-JNK and p-c-Jun in cultured astrocytes. SP600125 significantly inhibited LPS-induced increase in production of IL-1 (3. Conclusion This study indicates that pioglitazone can inhibit the expression of IL-1(3 induced by LPS in cultured astrocytes through the suppression of JNK signal transduction pathway activity.%目的 研究吡格列酮(Pio)对脂多糖 (LPS)诱导的星形胶质细胞白介素-1β(IL-1β)抑制作用及JNK信号传导通路对其的影响.方法 ELISA法测定培养液中IL-1β的含量;免疫荧光染色法观察星形胶质细胞IL-1β的蛋白表达;Western blot检测星形胶质细胞磷酸化JNK1和磷酸化c-Jun蛋白表达水平的改变.结果 星形胶质细胞在LPS (10 mg*L-1)刺激下IL-1β的含量、蛋白表达以及磷酸化JNK1、磷酸化c-Jun蛋白水平与正常对照组比较均增高.特异性JNK特异性阻断剂SP600125 (10.0 μmol*L-1)可明显抑制LPS引起的IL-1β产生增加;Pio (0.1、1.0、10.0 μmol*L-1)则可降低IL-1β产生,抑制IL-1β的蛋白表达及下调p-JNK1、p-c-Jun蛋白水平.结论 Pio能明显抑制LPS诱导的大鼠皮层星形胶质细胞IL-1β表达增加,这种作用可能与其下调JNK信号转导通路有关.