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.
Objective Exposure to air pollution, specifically to particulate matter (PM), is a significant global health hazard. Recent studies have shown that PM triggers NLRP3-mediated pyroptosis. However, whether cathepsin B (CTSB), a protease released from ruptured lysosomes, activates the NLRP3 inflammasome is unclear. This study investigated the involvement of CTSB and NLRP3 inflammasome activation in PM-exposed human vocal fold fibroblasts (hVFFs). Methods Pyroptotic cell death was evaluated based on LDH release and PI staining and NLRP3 inflammasome activation via western blotting and immunofluorescence staining. The inflammatory response during pyroptosis was analyzed in an ELISA assay and lysosomal stability by LysoTracker staining. Results PM exposure was shown to induce cell membrane rupture and pyroptosis in hVFFs, through a mechanism involving NLRP3, cleaved caspase-1, gasdermin D (GSDMD), IL-1β, lysosomal-associated membrane protein 2a, and CTSB. These results suggested that PM causes pyroptosis in hVFFs via NLRP3 inflammasome activation and lysosomal destabilization. Treatment of the PM-exposed cells with MCC950, an NLRP3-specific inhibitor, suppressed this pathway, providing further evidence of the involvement of the NLRP3 inflammasome in PM-induced pyroptosis. A role for CTSB in NLRP3 inflammasome activation and pyroptosis was implied by the finding that treatment with CA-074-me, a CTSB-specific inhibitor, reduced CTSB expression and suppressed NLRP3, cleaved caspase-1, GSDMD, IL-1β, and CTSB in PM-exposed hVFFs. Conclusions Our study shows that both the NLRP3 inflammasome and CTSB participate in PM-induced pyroptosis in hVFFs. Targeting these pathways could yield novel therapeutic agents able to mitigate the detrimental effects of PM exposure on respiratory health.
Chronic laryngitis is a persistent inflammatory disorder that has recently been linked to air pollution. Fine particulate matter (PM2.5) is a major air pollutant capable of inducing pyroptosis, a caspase-1-dependent inflammatory form of programmed cell death characterized by gasdermin D cleavage, plasma membrane rupture, and the release of proinflammatory cytokines. However, the mechanisms underlying PM2.5-induced pyroptosis in the larynx and the potential therapeutic strategies remain unclear. In this study, we investigated the protective effects of human turbinate mesenchymal stromal cell-derived exosomes (hTMSC-exos) on PM2.5-induced pyroptosis in human vocal fold fibroblasts (hVFFs). PM2.5 exposure triggered pyroptotic cell death, as evidenced by increased LDH release, PI positivity, GSDMD-N expression, and IL-1β and IL-18 secretion. It also induced excessive reactive oxygen species (ROS) production, disrupted mitochondrial function, and impaired mitophagy, as indicated by p62 accumulation and suppressed PINK1/Parkin expression. Treatment with hTMSC-exos significantly alleviated these effects, reducing pyroptosis markers, lowering ROS production, and preserving mitochondrial membrane potential. Mechanistically, hTMSC-exos restored mitophagy activity suppressed by PM2.5, as demonstrated by increased LC3-II, PINK1, and Parkin expression and decreased p62 levels. Fluorescence imaging further confirmed enhanced co-localization of mitochondria with LC3-II. Importantly, the protective effects of hTMSC-exos were abolished by the mitophagy-specific inhibitor cyclosporin A, confirming that mitophagy activation is essential for exosome-mediated protection. These findings suggest that hTMSC-exos attenuate PM2.5-induced pyroptosis through a mitophagy-dependent mechanism, providing new insight into the pathogenesis of environmentally induced laryngeal injury and highlighting the therapeutic potential of exosome-based approaches for chronic laryngitis.
Ved Batesiansk, Müllersk og andre former for mimicry efterligner en art en anden i form, farver alle dufte, hvorved det opnår en overlevelsesmæssig fordel – typisk ved at mindske risikoen for at blive ædt af rovdyr. Mimicry er opstået igennem naturlig selektion og blev i anden halvdel af 1800-tallet brugt til at sandsynliggøre evolutionsteorien.
