Celastrol Suppresses Morphological and Transcriptional Responses in Microglial Cells Upon Stimulation with Double-Stranded RNA
Celastrol Suppresses Morphological and Transcriptional Responses in Microglial Cells Upon Stimulation with Double-Stranded RNA
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DOI：
10.3109/00207451003615763
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发表时间：
2010-04
影响因子：
2.2
通讯作者：
K. Nakamichi;H. Kitani;Mutsuyo Takayama-Ito;K. Morimoto;I. Kurane;M. Saijo
中科院分区：
文献类型：
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作者：
K. Nakamichi;H. Kitani;Mutsuyo Takayama-Ito;K. Morimoto;I. Kurane;M. Saijo
尽管小胶质细胞在大脑免疫系统中起着关键作用，但越来越多的证据表明，过度的小胶质细胞激活会引起神经元和胶质细胞损伤，导致神经退行性和神经炎症性疾病。Celastrol是一种三萜，是一种有效的抗炎和抗氧化化合物，是从属于Celastraceae家族的多年生匍匐植物中提取的。在当前的研究中，我们分析了雷公藤红素在双链RNA刺激下对小胶质MG6细胞形态学和转录反应的影响，双链RNA是先天免疫细胞的强激活剂。在雷公藤红素的存在下，双链rna刺激的小胶质细胞的形态变化受到抑制。研究还发现，用celastrol治疗小胶质细胞导致双链rna诱导的促炎细胞因子和趋化因子的表达显著降低。这些数据表明，celastrol抑制小胶质细胞激活过程中的形态和转录反应。
ABSTRACT Despite the pivotal role of microglia in the immune system of the brain, a growing body of evidence suggests that excessive microglial activation provokes neuronal and glial damage, leading to neurodegenerative and neuroinflammatory disorders. Celastrol, a triterpene, is a potent anti-inflammatory and antioxidant compound derived from perennial creeping plants belonging to the Celastraceae family. In the current study, we have analyzed the effect of celastrol on morphological and transcriptional responses in microglial MG6 cells upon stimulation with double-stranded RNA, a strong activator of innate immune cells. In the presence of celastrol, morphological changes were inhibited in double-stranded RNA-stimulated microglia. It was also found that the treatment of microglia with celastrol led to a significant decrease in the double-stranded RNA-induced expression of proinflammatory cytokines and chemokines. These data demonstrate that celastrol inhibits morphological and transcriptional responses during microglial activation.