Minerva Medica 2020 Jun 02

DOI: 10.23736/S0026-4806.20.06652-5

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

PM2.5 promotes apoptosis of alveolar epithelial cells via targeting ROS/p38 signaling pathway and thus leads to emphysema in mice

Ruixue XIA ¹, Na FANG ², Yanjie YANG ², Feng XU ¹, Lingge ZHANG ², Shaoping JI ² ✉

¹ Department of Respiratory and Critical Care Medicine, Henan University Huaihe Hospital, Kaifeng, China; ² Cell Signal Transduction Laboratory and Institute of Biomedical Informatics, School of Basic Medical Sciences, Henan University, Kaifeng, China

BACKGROUND: To uncover the ability of PM2.5 exposure to induce apoptosis in alveolar epithelial cells by stimulating excessive production of reactive oxygen species (ROS), thus activating p38 to result in emphysema in mice.
METHODS: Male BALB / c mice with 6-8-week-old were exposed to 200 TPM mg/L PM2.5 for 12 weeks. Lung tissues of mice were harvested after sacrifice. H&E staining was conducted for observing alveolar structure change. Protein levels of p-p38 and p38, as well as ROS level in mouse liver tissues were determined. A549 cells were exposed to different doses of PM2.5, followed by ROS detection, protein level detection of p-p38 and p38, and apoptosis determination. After transfection of si-p38, protein level of clv-caspase3 and apoptotic rate in PM2.5-exposed A549 cells were assessed.
RESULTS: After 12-week exposure to PM2.5, enlarged alveolar space, elevated ROS level in lung tissues and activated p38 were observed in mice. In PM2.5-exposed A549 cells, ROS level, p-p38 expression and apoptotic rate were dose-dependently enhanced. The antioxidant NAC reversed the above changes in PM2.5-exposed A549 cells. Silence of p38 reversed the enhanced clv-claspase3 level and apoptotic rate in PM2.5-exposed A549 cells.
CONCLUSIONS: PM2.5 exposure elevates ROS level in lung tissues, and activates p38, thus leading to apoptosis of alveolar epithelial cells. PM2.5 finally results in the development of emphysema in mice.

KEY WORDS: PM2.5; ROS; p38; Apoptosis; Emphysema