Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells.

Exposure to particulate matter (PM) from ambient air pollution is a well-known risk factor for many lung diseases, but the mechanism(s) for this is not completely understood. Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (<2.5 µm) PM (PM_2.5). Although some of these changes have been reported in other studies, a comparison of how different concentrations and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. Here, we exposed BEAS-2B, a bronchial epithelial cell line, to different concentrations of PM_2.5, and compared how single or repeated doses of PM_2.5 affect both the transcriptome and methylome of cells. Widespread changes in gene expression occurred after cells were exposed to a single treatment of high-concentration (30 µg/cm²) PM_2.5 for 24 h. These genes were enriched in pathways regulating cytokine-cytokine interactions, Mitogen-Activated Protein Kinase (MAPK) signaling, PI3K-Akt signaling, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes, with just a slightly greater trend toward overall hypomethylation across the genome. Cells exposed to a lower concentration (1 µg/cm²) of PM_2.5 demonstrated a comparable, but more attenuated change in gene expression compared to cells exposed to higher concentrations. There were also many genes affected by lower concentrations of PM_2.5, but not higher concentrations. Additionally, repeated exposure to PM_2.5 (1 µg/cm²) for seven days resulted in transcriptomic and DNA methylomic changes that were distinct from cells treated with PM_2.5 for only one day. Compared to single exposure, repeated exposure to PM_2.5 caused a more notable degree of hypomethylation across the genome, though certain genes and regions demonstrated increased DNA methylation. The overall increase in hypomethylation, especially with repeated exposure to PM_2.5, was associated with an increase in expression of ten-eleven translocation enzymes. These data demonstrate how variations in concentration and duration of PM_2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells, which may have important implications in the development of both acute and chronic lung disease.