Particulate matter exposure induces the autophagy of macrophages via oxidative stress-mediated PI3K/AKT/mTOR pathway. (January 2017) - Su, Ruijun
Abstract: Many epidemiological investigations have consistently demonstrated the immunotoxicity of fine particulate matter (PM2.5 ), but the underlying molecular mechanism remains unclear and needs to be elucidated. In this work, the immune cells, including pulmonary macrophages of SD rats and Raw264.7 cells, were applied to further investigate the effect of PM2.5 on cell autophagy of macrophages, thus clarified the possible molecular mechanism of immunotoxicity caused by PM2.5 . SD rats were exposed to summer (0.2, 0.6, 1.5 mg kg −1 b.w.) and winter (0.3, 1.5, 2.7 mg kg −1 b.w.) PM2.5 adopting the intratracheal instillation method. The exposure was performed one time every 3 days and continued for 2 months. The data showed that PM2.5 exposure decreased numbers of immune cells in pulmonary macrophages of SD rats. In addition, PM2.5 could induce the cell autophagy through the increased LC3 and decreased p62 mRNA and protein levels of pulmonary macrophages in SD rats and Raw264.7 cells in a concentration-dependent manner. Strikingly, PM2.5 -induced oxidative stress was observed. However, NAC supplement (the ROS inhibitor) significantly reversed PM2.5 -caused effects. Additionally, the PI3K/AKT/mTOR pathway was activated in PM2.5 -treated cells and NAC had an important inhibitory effect. These results demonstrated that PM2.5 exposures induced autophagy of pulmonary macrophages via the oxidative stress-mediated PI3K/AKT/mTOR pathway, which may contribute to explain the molecular mechanism of immunotoxicity caused by PM2.5 and provide the theoretical foundation for environment toxicology of PM2.5 . Graphical abstract: Image 1 Highlights: PM2.5 exposure decreased numbers of immune cells in SD rats BALF. PM2.5 could induce the autophagy of pulmonary macrophages in SD rats and Raw264.7 cells. PM2.5 exposure led to the activation of oxidative stress in Raw264.7 cells. PM2.5 induced cell autophagy via the oxidative stress-mediated PI3K/AKT/mTOR pathway.