Airborne fine particulate matter induces multiple cell death pathways in human lung epithelial cells

摘要: Our group was the first one reporting that autophagy could be triggered by airborne fine particulate matter (PM) with a mean diameter of less than 2.5 μm (PM2.5) in human lung epithelial A549 cells, which potentially lead to cell death. In present study, we further explored potential interactions between and apoptosis because it well documented PM2.5 induce cells. Much our surprise, found PM2.5-exposure caused oxidative stress, resulting activation multiple death pathways is, tumor necrosis factor-alpha (TNF-α)-induced pathway as evidenced TNF-α secretion caspase-8 -3, intrinsic increased expression pro-apoptotic protein Bax, decreased anti-apoptotic Bcl-2, disruption mitochondrial membrane potential, caspase-9 an number double-membrane vesicles, accompanied increases conversion punctuation microtubule-associated proteins light chain 3 (LC3) Beclin 1. It appears reactive oxygen species (ROS) function signaling molecules for all three pretreatment N-acetylcysteine, scavenger ROS, almost completely abolished significantly reduced apoptotic autophagic another aspect, inhibiting 3-methyladenine, specific inhibitor, enhanced PM2.5-induced cytotoxicity. Intriguingly, neutralization anti-TNF-α special antibody not only caspase-8, but also drastically LC3-II conversion. Thus, study has provided novel insights into mechanism cytotoxicity even pathogenesis diseases associated exposure.