Xiujian Xu1, Liang Zhang2, Xinchun Ye3, Qi Hao2, Tao Zhang2, Guiyun Cui4, Ming Yu5. 1. Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, Jiangsu, China. 2. Xuzhou Medical University, Xuzhou, Jiangsu, China. 3. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221006, Jiangsu, China. 4. Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221006, Jiangsu, China. cuiguiyun_js@126.com. 5. Department of Neurology, The Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, 212001, Jiangsu, China. yuming_js@163.com.
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.
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.
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