The Effect of Hypoxia on Diesel Exhaust Particle Toxicity in Lung Epithelial Cells

Hypoxia is characterised by tissue oxygen concentrations below 2% and occurs in several pathologies including neurodegenerative and chronic lung diseases. Air pollution and its major component, particulate matter, are also a public health concern and are directly implicated in the onset of chronic lung disease. Therefore, an understanding of the effects of hypoxia on the susceptibility of lung tissues to air pollutants is crucial. In this study we investigate the effects of hypoxia on the toxicity of diesel exhaust particles (DEP) in two lung epithelial cells: human and rat type II alveolar cells. The goal is to discern whether hypoxia exacerbates the toxic response to DEP exposure in both 24-hour and 48-hour exposures. We subjected both cell lines to increasing concentrations of DEP for 24 and 48 hours in both normoxic and hypoxic (2% oxygen) incubation conditions and measured the rate of cell death, proliferation, and pro-inflammatory cytokine and chemokine production. The results indicate that hypoxia increases DEP cytotoxicity in RLE6TN but not A549 cells, and that hypoxia decreases the production of pro-inflammatory markers induced by exposure to DEP. These results suggest an increased susceptibility to particulate matter toxicity when prolonged or chronic hypoxia is present.