法苏迪尔
神经炎症
炎症
小胶质细胞
化学
Rho相关蛋白激酶
愤怒(情绪)
信号转导
糖基化
药理学
一氧化氮合酶
癌症研究
受体
细胞生物学
一氧化氮
免疫学
医学
生物
生物化学
神经科学
有机化学
作者
Jingkao Chen,Zhaowei Sun,Minghua Jin,Yalin Tu,Shengnan Wang,Xiaohong Yang,Qiuhe Chen,Xiao Zhang,Yifan Han,Rongbiao Pi
标识
DOI:10.1016/j.jneuroim.2017.02.010
摘要
The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells. AGEs could activate ROCK pathway in a concentration-dependent manner. ROCK inhibitor fasudil and RAGE-specific blocker FPS-ZM1 significantly inhibited AGEs-mediated activation of BV2 cells and induction of reactive oxygen species (ROS). FPS-ZM1 and fasudil exerted their anti-inflammatory effects by downregulating inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NLRP3 and nuclear translocation of nuclear factor kappa B (NF-κB) p65. In addition, AGEs induced both M1 (CD16/32, M1 marker) and M2 (CD206, M2 marker) phenotype in BV2 cells. Fasudil and FPS-ZM1 led to a decreased M1 and increased M2 phenotype. Together, these results indicate that the AGEs/RAGE/Rho/ROCK pathway in BV2 cells could intensify the non-specific inflammation of AD, which will provide novel strategies for the development of anti-AD drugs.
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