Polystyrene Nanoplastics Induce Inflammasome Activation in Nasal Epithelial Cells via ROS-Mediated Mitochondrial...

Nanoplastics are emerging airborne pollutants capable of reaching the nasal cavity. However, their effects on nasal epithelial health remain poorly understood. This study investigated how polystyrene (PS) nanoplastics affect nasal epithelial cells, focusing on NOD-like receptor protein 3 (NLRP3) inflammasome activation, oxidative stress, and mitochondrial injury. Human RPMI 2650 nasal epithelial cells were exposed to PS nanoplastics at various concentrations for 24 h. Cellular responses were evaluated by assessing viability, inflammasome protein expression, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and adenosine triphosphate (ATP) levels using colorimetric assays, Western blotting, and flow cytometry. Mitochondrial ROS was analyzed with MitoSOX, and mitochondrial regulators sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) were examined to clarify underlying mechanisms. The antioxidant N-acetylcysteine (NAC) was used to assess the role of oxidative stress. PS exposure reduced cell viability and increased the expression of inflammasome-related proteins including NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and cleaved caspase-1. Protein levels peaked at moderate concentrations and declined at higher doses, suggesting a progression toward pyroptosis. These alterations were accompanied by increased intracellular and mitochondrial ROS, mitochondrial depolarization, decreased ATP levels, and downregulation of SIRT1 and AMPK. NAC pretreatment mitigated ROS accumulation, alleviated mitochondrial impairment, and attenuated inflammasome activation. PS induce oxidative stress, mitochondrial impairment, and dysregulation of SIRT1-AMPK signaling, collectively promoting inflammasome activation in nasal epithelial cells. These findings highlight potential health risks of inhaled nanoplastics and underscore the need for further investigation into antioxidant-based protective strategies.