The effect of exposure time and concentration of airborne PM_2.5 on lung injury in mice: A transcriptome analysis

The association between airborne fine particulate matter (PM_2.5) concentration and the risk of respiratory diseases has been well documented by epidemiological studies. However, the mechanism underlying the harmful effect of PM_2.5 has not been fully understood. In this study, we exposed the C57BL/6J mice to airborne PM_2.5 for 3 months (mean daily concentration ~50 or ~110 μg/m³, defined as PM_2.5-3L or PM_2.5-3H) or 6 months (mean daily concentration ~50 μg/m³, defined as PM_2.5-6L) through a whole-body exposure system. Histological and biochemical analysis revealed that PM_2.5-3H exposure caused more severe lung injury than did PM_2.5-3L, and the difference was greater than that of PM_2.5-6L vs PM_2.5-3L exposure. With RNA-sequencing technique, we found that the lungs exposed with different concentration of PM_2.5 have distinct transcriptional profiles. PM_2.5-3H exposure caused more differentially expressed genes (DEGs) in lungs than did PM_2.5-3L or PM_2.5-6L. The DEGs induced by PM_2.5-3L or PM_2.5-6L exposure were mainly enriched in immune pathways, including Hematopoietic cell lineage and Cytokine-cytokine receptor interaction, while the DEGs induced by PM_2.5-3H exposure were mainly enriched in cardiovascular disease pathways, including Hypertrophic cardiomyopathy and Dilated cardiomyopathy. In addition, we found that upregulation of Cd5l and reduction of Hspa1 and peroxiredoxin-4 was associated with PM_2.5-induced pulmonary inflammation and oxidative stress. These results may provide new insight into the cytotoxicity mechanism of PM_2.5 and help to development of new strategies to attenuate air pollution associated respiratory disease.