Polychlorinated biphenyl quinone induces caspase 1-mediated pyroptosis through the induction of pro-inflammatory HMGB1-TLR4-NLRP3-GSDMD signal axis

Polychlorinated biphenyls (PCBs) are one of the most refractory environmental pollutants. For their ubiquitous existence in the biological systems (including human body), it is important to investigate their toxic behavior. Our previous findings demonstrated that a high reactive metabolite of PCB, namely PCB29-pQ, causes several programmed cell death (PCD), such as intrinsic/extrinsic apoptosis and autophagic cell death. The mechanistic study suggested the toxic actions of PCB29-pQ is largely related to its reactive oxygen species (ROS)-generation ability. Pyroptosis is a caspase 1-mediated pro-inflammatory PCD which was discovered recently. The aim of this study is to seek the linkage of pyroptosis between PCB29-pQ exposures. We first confirmed that PCB29-pQ stimulates Hela cells to produce excess amounts of ROS. Then, we found PCB29-pQ activates NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome that mediates caspase 1 activation. The activated caspase 1 (cleaved caspase 1) promotes gasder...