Paraquat mediates BV-2 microglia activation by raising intracellular ROS and inhibiting Akt1 phosphorylation

Abstract

Microglia is the innate immune cell in central nervous system (CNS) and plays an important role in neuroinflammation. Microglia mediated neuroinflammation is the key factor affecting the development of neurodegenerative diseases. Although there was evidence that paraquat (PQ) could induce inflammatory response, its mechanism was not clear. The present study investigated the mechanisms of PQ-induced inflammatory responses in BV-2 microglia cells, and tried to reveal the role of ROS/Akt1 pathway. The results showed that the cell activation markers (iNOS and CD206) of BV-2 cells were increased after PQ treatment, suggesting that BV-2 microglia were activated. PQ induced the reactive oxygen species (ROS) and inhibited the AKT1 phosphorylation in BV-2 cells. Besides, the M1 markers expression (IL-6, TNF-α and IL-1β) were significantly increased after PQ treatment, which suggested that PQ induced the increase of M1 phenotype of BV-2 microglia. Pre-treated with NAC (ROS scavenger), the M1 phenotype was decreased while the p-Akt1 was restored compared to PQ stimulation. Furthermore, we built an Akt1(S473E)-overexpression BV-2 cell line. The Akt1 (S473E) partially attenuated the PQ induced increase in M1 phenotype, while ROS did not significantly change. These results indicated that PQ induced BV-2 microglia activation by increased ROS mediated Akt1 activation inhibition, leading to neuroinflammation.

Keywords: Akt1; BV-2 microglia; M1/M2 phenotype; Paraquat; ROS.