Nrf2/ARE pathway inhibits ROS-induced NLRP3 inflammasome activation in BV2 cells after cerebral ischemia reperfusion

Abstract

Objective: Current therapies for ischemia/reperfusion are insufficient because of our poor understanding of the mechanisms of brain injury after ischemic stroke. As a vital component of the innate immune system, NLRP3 inflammasome contributes to ischemic brain injury; however, a detailed understanding of their molecular mechanisms is unknown. This study was designed to investigate the effect of nuclear factor E2-related factor-2 (Nrf2) on NLRP3 inflammasome.

Materials and methods: BV2 microglial cells were pretreated with tert-butylhydroquinone or Nrf2 CRISPR plasmid before oxygen-glucose deprivation/reoxygenation (OGDR) exposure. Then we observed the effect of Nrf2 on NLRP3 inflammasome.

Results: We identified that Nrf2 activation inhibited NLRP3 inflammasome expression and subsequent IL-1β generation. Furthermore, the activation of NLRP3 inflammasome was sensitive to the reactive oxygen species (ROS) level and Nrf2 could decrease the production of ROS. Additionally, as a Nrf2-targeted ARE gene, NADPH quinone oxidoreductase 1 was involved in the inhibition of the NLRP3 inflammasome.

Conclusion: We elucidated an inhibitory regulation of Nrf2/ARE pathway on ROS-induced NLRP3 inflammasome activation in BV2 microglial cells after OGDR exposure.

Keywords: Ischemia/reperfusion; NLRP3 inflammasome; Nrf2; ROS.