2. Academic Validation
  3. ROS-induced NLRP3 inflammasome priming and activation mediate PCB 118- induced pyroptosis in endothelial cells

ROS-induced NLRP3 inflammasome priming and activation mediate PCB 118- induced pyroptosis in endothelial cells

  • Ecotoxicol Environ Saf. 2020 Feb;189:109937. doi: 10.1016/j.ecoenv.2019.109937.
Yang Long 1,  Xin Liu 2,  Xiao-Zhen Tan 2,  Chun-Xia Jiang 3,  Shao-Wei Chen 4,  Guan-Nan Liang 2,  Xue-Mei He 2,  Jian Wu 2,  Tao Chen 5,  Yong Xu 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China; Laboratory of Endocrinology, Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • 2 Laboratory of Endocrinology, Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • 3 Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • 4 Medical Reproduction Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
  • 5 Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, PR China. Electronic address: dr.chentao@qq.com.
  • 6 Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, PR China; Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, Sichuan, PR China. Electronic address: xywyll@aliyun.com.
PMID: 31785945 DOI: 10.1016/j.ecoenv.2019.109937
Abstract

Growing epidemiological evidence has shown that exposure to polychlorinated biphenyls (PCBs) is harmful to the cardiovascular system. However, how PCB 118-induced oxidative stress mediates endothelial dysfunction is not fully understood. Here, we explored whether and how PCB 118 exposure-induced oxidative stress leads to NLRP3 inflammasome-dependent Pyroptosis in endothelial cells. As expected, PCB 118 was cytotoxic to HUVECs and induced Caspase-1 activation and cell membrane disruption, which are characteristics of Pyroptosis. Moreover, PCB 118-induced Pyroptosis may have been due to the activation of the NLRP3 infammasomes. PCB 118 also induced excessive Reactive Oxygen Species (ROS) in HUVECs. The ROS scavenger (±)-α-tocopherol and the NFκB inhibitor BAY11-7082 reversed the upregulation of NLRP3 expression and the increase in NLRP3 inflammasome activation induced by PCB 118 exposure in HUVECs. Additionally, PCB 118-induced oxidative stress and Pyroptosis were dependent on Aryl Hydrocarbon Receptor (AhR) activation and subsequent Cytochrome P450 1A1 upregulation, which we confirmed by using the AhR selective antagonist CH 223191. These data suggest that PCB 118 exposure induces NLRP3 inflammasome activation and subsequently leads to Pyroptosis in endothelial cells in vitro and in vivo. AhR-mediated ROS production play a central role in PCB 118-induced Pyroptosis by priming NFκB-dependent NLRP3 expression and promoting inflammasome activation.

Keywords

2,3′,4,4′,5 pentachlorobiphenyl; Endothelial dysfunction; NLRP3 inflammasome; Polychlorinated biphenyls; Pyroptosis; Reactive oxygen species.

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