Inhibition of AGEs/RAGE/Rho/ROCK.pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway
Inhibition of AGEs/RAGE/Rho/ROCK.pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway
复制标题
抑制 AGEs/RAGE/Rho/ROCK. 通路通过 NF-kappa B 通路调节 BV2 小胶质细胞 M1/M2 极化来抑制非特异性神经炎症
DOI：
10.1016/j.jneuroim.2017.02.010
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发表时间：
2017-04-15
影响因子：
3.3
通讯作者：
Pi, Rongbiao
中科院分区：
文献类型：
--
作者：
Chen, Jingkao;Sun, Zhaowei;Pi, Rongbiao
小胶质细胞介导的神经炎症在阿尔茨海默病(AD)的发病机制中起着重要作用。晚期糖基化终产物(AGEs)/晚期糖基化终产物受体(RAGE)或Rho/Rho激酶(ROCK)都参与了非特异性炎症的发生。然而，关于它们对神经炎症的影响的报道很少。在这里，我们探讨了AGEs/RAGE/Rho/ROCK通路在BV2细胞非特异性炎症和小胶质细胞极化中的作用机制。AGEs以浓度依赖的方式激活岩石通路。ROCK阻滞剂法舒地尔和RAGE特异性阻断剂FPS-ZM1显著抑制AGEs介导的BV2细胞活化和ROS的诱导。FPS-ZM1和Fasudil通过下调诱导型一氧化氮合酶(INOS)、环氧合酶-2(COX-2)、NLRP3和核因子kappaB核转位p65发挥抗炎作用。此外，AGEs还诱导BV2细胞的M1(CD16/32，M1标志物)和M2(CD206，M2标志物)表型。法舒地尔和FPS-ZM1导致M1减少，M2表型增加。这些结果表明，BV2细胞中的AGEs/RAGE/Rho/ROCK通路可加重AD的非特异性炎症反应，这将为抗AD药物的开发提供新的策略。(C)2017爱思唯尔B.V.保留所有权利。
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 blacker 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-KB) 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. (C) 2017 Elsevier B.V. All rights reserved.