Particulate matter exposure induces the autophagy of macrophages via oxidative stress-mediated PI3K/AKT/mTOR pathway

Abstract

Many epidemiological investigations have consistently demonstrated the immunotoxicity of fine particulate matter (PM_2.5), 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 PM_2.5 on cell autophagy of macrophages, thus clarified the possible molecular mechanism of immunotoxicity caused by PM_2.5. 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.) PM_2.5 adopting the intratracheal instillation method. The exposure was performed one time every 3 days and continued for 2 months. The data showed that PM_2.5 exposure decreased numbers of immune cells in pulmonary macrophages of SD rats. In addition, PM_2.5 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, PM_2.5-induced oxidative stress was observed. However, NAC supplement (the ROS inhibitor) significantly reversed PM_2.5-caused effects. Additionally, the PI3K/AKT/mTOR pathway was activated in PM_2.5-treated cells and NAC had an important inhibitory effect. These results demonstrated that PM_2.5 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 PM_2.5 and provide the theoretical foundation for environment toxicology of PM_2.5.

Keywords: Autophagy; Oxidative stress; PI3K/AKT/mTOR pathway; PM(2.5); Pulmonary macrophage.