The suppressive effects of gx-50 on A尾-induced chemotactic migration of microglia

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• 作者：Yubing Guo ; Shi Shi ; Maoping Tang ; Dongli Liang ; Wangjie Xu ; Lianyun Wang ; Zhaoxia Wang ; ^{zhaoxiaw@sjtu.edu.cn" class="auth_mail} ; Zhongdong Qiao ; ^{zdqiao@sjtu.edu.cn" class="auth_mail}
• 关键词：Alzheimer's disease ; Microglia ; Chemotaxis ; TGF-尾1-Smad2 pathway
• 刊名：International Immunopharmacology
• 出版年：April, 2014
• 年：2014
• 卷：19
• 期：2
• 页码：283-289
• 全文大小：1374 K

文摘

Microglia, the main immune cells of the central nervous system (CNS), play a vital role in the development of AD. Once microglia are activated, they migrate to neuritic plaques and persistently release pro-inflammatory mediators that lead to neuroinflammation and neuronal degeneration, accelerating the progression of AD. In this study, we analyzed whether an AD candidate drug, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-phenyl-acrylamide (gx-50), a compound extracted from Sichuan pepper (Zanthoxylum bungeanum), exhibited suppressive effects on the chemotactic migration of microglia induced by A尾. At first, the effects of gx-50 on the migration of primary cultured microglia to A尾 were detected by transwell assay, and the secretion of chemokine CCL5 was measured by ELISA assay. Then, the release of TGF-尾1 was detected by ELISA and quantitative real-time PCR, and the activation of the TGF-尾1-Smad2 pathway was analyzed by Western blotting. The LDH assay revealed that cell viability was not affected by gx-50 at concentrations from 0.01 to 100 渭M; thus, combined with our previous studies, 1 渭M was chosen as the treatment concentration. The cell transwell measurement demonstrated that gx-50 suppressed the chemotactic migration of microglia by nearly 50% and inhibited the increase in CCL5 triggered by A尾. Moreover, the analysis of the TGF-尾1-Smad2 pathway revealed that gx-50 can antagonize A尾-induced down-regulation of TGF-尾1 at both the mRNA and protein levels and stimulate the signal pathway activation. Simultaneously, gx-50 pretreatment also significantly enhanced the phosphorylation of glycogen synthase kinase-3尾 (GSK-3尾), which correlated closely with the migration of microglia. In conclusion, in the presence of A尾, gx-50 pretreatment inhibited the excessive chemotactic migration of microglia.