PhotoagedPolyvinyl Chloride Microplastics AggravateAirway Epithelial Barrier Dysfunction via TXNIP–NLRP3-MediatedInflammatory Amplification

Abstract Microplastics are ubiquitous in the atmosphere and may be inhaled into the respiratory system to cause adverse health effects. Photoaging of microplastics in the atmosphere is inevitable, which changes their toxic effects greatly, yet the impacts and underlying mechanisms remain poorly understood. In this study, poly(vinyl chloride) microplastics (PVC-MPs), commonly detected in the atmosphere, were selected to investigate the effects of photoaging on pulmonary toxicological responses at 7 days after a single intratracheal instillation in a mouse model. Photoaging enhanced the abundance of oxygen-containing functional groups on the particle surface, surface hydrophilicity, and oxidative potential. Upon a short-term intratracheal exposure, photoaged PVC-MPs (A-PVC) induced more severe pulmonary inflammation and epithelial barrier dysfunction than the virgin PVC-MPs (V-PVC), as evidenced by increased protein leakage and lactate dehydrogenase release in bronchoalveolar lavage fluid and disruption of tight junction proteins. Transcriptomic analysis revealed enrichment of the NOD-like receptor signaling pathway and activated TXNIP–NLRP3 inflammasome axis. In vitro tests with BEAS-2B cells indicated that more A-PVC was adsorbed on the cell membrane, likely due to increased membrane affinity than V-PVC, thus triggering excessive ROS generation and leading to TXNIP-dependent NLRP3 activation and tight junction disruption. Inhibition of ROS, TXNIP, or NLRP3 attenuated inflammasome activation and preserved barrier integrity. These findings demonstrate that environmental photoaging exacerbated short-term pulmonary toxicity of PVC-MPs through a ROS–TXNIP–NLRP3-mediated inflammatory amplification axis.