Temporal analysis of lung injury induced by real-ambient PM 2 .5 exposure in mice.

Fine particulate matter (PM 2.5 ) has been shown to induce lung injury. However, the pathophysiological mechanisms of PM 2.5 -induced pulmonary injury after different exposure times are poorly understood. In this study, we exposed male ICR mice to a whole-body PM 2.5 inhalation system at daily mean concentration range from 92.00 to 862.00 μg/m 3 for 30, 60, and 90 days. We found that following prolonged exposure to PM 2.5 , pulmonary injury was increasingly evident with significant histopathological alterations. Notably, the pulmonary inflammatory response and fibrosis caused by PM 2.5 after different exposure times were closely associated with histopathological changes. In addition, PM 2.5 exposure caused oxidative stress, DNA damage and impairment of DNA repair in a time-dependent manner in the lung. Importantly, exposure to PM 2.5 eventually caused apoptosis in the lung through upregulation of cleaved-caspase-3 and downregulation of Bcl-2. Overall, our data demonstrated that PM 2.5 led to pulmonary injury in a time-dependent manner via upregulation of proinflammatory and fibrosis-related genes, and activation of the DNA damage response. Our findings provided a novel perspective on the pathophysiology of respiratory diseases caused by airborne pollution.