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/m(3), defined as PM(2.5)–3L or PM(2.5)–3H) or 6 months (mean daily concentration ~50 μg/m(3), 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.