Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage

• Published in: Particle and fibre toxicology 2023-01, Vol.20 (1), p.2-17, Article 2
• Main Authors: Woo, Jong-Hwan, Seo, Hyeon Jin, Lee, Jun-Young, Lee, Iljung, Jeon, Kisoo, Kim, Bumseok, Lee, Kyuhong
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - metabolism; Inflammation - chemically induced; Inflammation - metabolism; Mice; Microplastic; Microplastics - toxicity; Mitochondrial damage; Nanoplastic; NF-kappa B - metabolism; NF-κB; p38; Pneumonia - chemically induced; Polypropylene (PP); Polypropylenes - toxicity; Reactive Oxygen Species - metabolism
• ISSN: 1743-8977; 1743-8977
• DOI: 10.1186/s12989-022-00512-8

Polypropylene (PP) is used in various products such as disposable containers, spoons, and automobile parts. The disposable masks used for COVID-19 prevention mainly comprise PP, and the disposal of such masks is concerning because of the potential environmental pollution. Recent reports have suggested that weathered PP microparticles can be inhaled, however, the inhalation toxicology of PP microparticles is poorly understood. Inflammatory cell numbers, reactive oxygen species (ROS) production, and the levels of inflammatory cytokines and chemokines in PP-instilled mice (2.5 or 5 mg/kg) increased significantly compared to with those in the control. Histopathological analysis of the lung tissue of PP-stimulated mice revealed lung injuries, including the infiltration of inflammatory cells into the perivascular/parenchymal space, alveolar epithelial hyperplasia, and foamy macrophage aggregates. The in vitro study indicated that PP stimulation causes mitochondrial dysfunction including mitochondrial depolarization and decreased adenosine triphosphate (ATP) levels. PP stimulation led to cytotoxicity, ROS production, increase of inflammatory cytokines, and cell deaths in A549 cells. The results showed that PP stimulation increased the p-p38 and p-NF-κB protein levels both in vivo and in vitro, while p-ERK and p-JNK remained unchanged. Interestingly, the cytotoxicity that was induced by PP exposure was regulated by p38 and ROS inhibition in A549 cells. These results suggest that PP stimulation may contribute to inflammation pathogenesis via the p38 phosphorylation-mediated NF-κB pathway as a result of mitochondrial damage.