Diesel exhaust particle exposure accelerates oxidative DNA damage and cytotoxicity in normal human bronchial epithelial cells through PD-L1. (15th January 2023) - Kwon, Minji
Abstract: Diesel exhaust particles (DEPs) are a major cause of cancer progression as well as a variety of acute and chronic diseases. It is well-known that programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can induce immune escape in tumor cells. However, the function of PD-L1 in bronchial epithelial cells or how PD-L1 relates to cellular oxidation under DEPs-mediated oxidative stress is not well known. In this study, we investigated how PD-L1 affected DEPs-induced oxidative stress and cytotoxicity in human bronchial epithelial (HBE) cells, Beas-2B. DEPs not only induced intracellular reactive oxygen species (ROS) production, but also increased PD-L1 expression in HBE cells. Beas-2B cells overexpressing PD-L1 showed higher levels of ROS production, DNA damage, and apoptosis after DEPs treatment compared to control cells. In particular, the expression of an antioxidant enzyme heme-oxygenase-1 (HO-1) and nuclear translocation and transcriptional activity of Nrf2, a major regulator of HO-1, were lower in Beas-2B overexpressing PD-L1 cells than in control cells. DEPs-induced ROS generation, DNA damage and apoptosis in Beas-2B cells overexpressing PD-L1 were significantly restored by overexpressing HO-1. Collectively, our results suggest that DEPs can increase the expression of PD-L1 in HBE cells and that overexpressing PD-L1 might eventually promote DEPs-induced oxidative DNA damage and apoptosis. Graphical abstract: Image 1 Highlights: DEPs increase PD-L1 expression in human bronchial epithelial cells. Beas-2B-PD-L1 cells show accelerated cytotoxicity after DEPs exposure. Antioxidant systems regulated by Nrf2 are suppressed in Beas-2B-PD-L1 cells. DEPs-induced cytotoxicity is restored by HO-1 overexpression in Beas-2B-PD-L1 cells.