Abstract
Exposure to diesel exhaust particles (DEPs) has been associated with increased incidence of cardiopulmonary diseases. This study is aimed at examining the proinflammatory effects of DEP on primary human peripheral blood mononuclear cells (PBMC) and the underlying mechanisms using a human mononuclear cell line, THP-1. DEPs were incubated with the PBMC and THP-1 cells for 24 h, respectively. The supernatants were collected and subjected to measurement of proinflammatory mediators including interleukin 8 (IL-8) or tumor necrosis factor α (TNFα) by ELISA. Levels of reactive oxygen species (ROS) were determined using flow cytometry. Phosphorylation of the epidermal growth factor receptor (EGFR) was examined with immunoblotting. Exposure to DEP induced a concentration-dependent increase in the expression of IL-8 and TNFα in the PBMC and THP-1 cells. Further mechanistic studies with THP-1 cells indicated that DEP stimulation increased intracellular levels of ROS, an indicator of oxidative stress, and phosphorylation of the EGFR, indicative of EGFR activation. Pretreatment of THP-1 cells with the antioxidant N-acetyl-L-cysteine (NAC) markedly blunted DEP-induced EGFR phosphorylation, indicating that oxidative stress was involved in DEP-induced EGFR activation. Furthermore, the pretreatment of THP-1 cells with either NAC or a selective EGFR inhibitor significantly blocked DEP-induced IL-8 expression, implying that oxidative stress and subsequent EGFR activation mediated DEP-induced inflammatory response. In summary, DEP stimulation increases the expression of proinflammatory mediators in human mononuclear cells, which is regulated by oxidative stress-EGFR signaling pathway.
Highlights
Exposure to air pollution, especially airborne particulate matter (PM), has been associated with increased morbidity and mortality for cardiopulmonary diseases [1,2,3,4,5,6]
Exposure of the peripheral blood mononuclear cells (PBMC) to 10-100 μg/ml for 24 h did not result in significant alterations in cytotoxicity, as assessed by assay of Lactate dehydrogenase (LDH) activity released into the culture medium
Under the same exposure condition, diesel exhaust particles (DEPs) treatment increased the expression of proinflammatory mediators including interleukin 8 (IL-8) and tumor necrosis factor α (TNFα) in the PBMC from Acute coronary syndrome (ACS) patients
Summary
Especially airborne particulate matter (PM), has been associated with increased morbidity and mortality for cardiopulmonary diseases [1,2,3,4,5,6]. Given the significant contribution of PM emissions from diesel vehicles to the total concentration of PM in ambient air, Mediators of Inflammation much research has been carried out on effects of DEP that have been used as the surrogate in exploring the mechanisms by which airborne fine or ultrafine particles promote cardiopulmonary diseases [9]. Peripheral leukocytes play an important role in the inflammatory response, interact with the endothelium in controlling vascular homeostasis, and are involved in the initiation of atherogenesis [15, 16] In this context, this study is aimed at examining the proinflammatory effects of DEP on human peripheral blood mononuclear cells (PBMC) and the underlying mechanisms using THP-1 cells
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have