Polystyrene nanoplastics aggravate house dust mite induced allergic airway inflammation through EGFR/ERK-dependent lung epithelial barrier dysfunction

Abstract

Concerns that airborne micro- and nanoplastics (MNPs) may impair human respiratory health are rising. However, the specific effects of MNPs on allergic asthma remain insufficiently explored. This study developed an allergic asthma model using house dust mite (HDM), and mice were exposed to 50 μg polystyrene nanoparticles (PS-NPs) at three-days interval. Additionally, the effects and potential mechanisms of PS-NPs exposure (25, 50 and 100 μg/mL) on lung epithelial barrier dysfunction were explored using mouse lung epithelial type II (MLE-12) and A549 cells. The pathological changes of airway tissue and the increase of inflammatory response confirmed that exposure to PS-NPs significantly aggravated allergic asthma in mice. Importantly, in the presence of HDM sensitization, the accumulation of PS-NPs in the alveolar region was increased, leading to lung epithelial barrier dysfunction and more Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-13, immunoglobulin E (Ig E) and eosinophils. The activation of the epidermal growth factor receptor (EGFR) pathway and its downstream extracellular regulating kinase (ERK) was investigated using transcriptomic sequencing to elucidate the effects of PS-NPs exposure on lung epithelial barrier dysfunction. Furthermore, an EGFR-specific inhibitor AG1478 was employed to confirm the role of the EGFR/ERK pathway in lung epithelial barrier dysfunction and asthma exacerbation in vitro and in vivo experiments. In conclusion, the molecular mechanism by which PS-NPs aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PS-NPs and lays a theoretical foundation for addressing the health risks posed by PS-NPs.