Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 305, Issue -, Pages 108-114Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2017.02.010
Keywords
Alzheimer's disease; BV2 cells; Neuroinflammation; Advanced glycation end products; Rho kinase
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Funding
- Guangdong Provincial International Cooperation Project of Science Technology [2013B051000038]
- National Natural Science Foundation of China [31371070, 81671264]
- Science and Technology Project of Guangdong Province [2016A070712004]
- Fundamental Research Funds for the Central Universities [15ykjc08b]
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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.
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