Exposure effects beyond the epithelial barrier: trans-epithelial induction of oxidative stress by diesel exhaust particulates in lung fibroblasts in an organotypic human airway model

In vitro bronchial epithelial monoculture models have been pivotal in defining the adverse effects of inhaled toxicant exposures; however, they are only representative of one cellular compartment and may not accurately reflect the effects of exposures on other cell types. Lung fibroblasts exist immediately beneath the bronchial epithelial barrier and play a central role in lung structure and function, as well as disease development and progression. We tested the hypothesis that in vitro exposure of a human bronchial epithelial cell barrier to the model oxidant diesel exhaust particulates caused trans-epithelial oxidative stress in the underlying lung fibroblasts using a human bronchial epithelial cell and lung fibroblast co-culture model. We observed that diesel exhaust particulates caused trans-epithelial oxidative stress in underlying lung fibroblasts as indicated by intracellular accumulation of the reactive oxygen species hydrogen peroxide, oxidation of the cellular antioxidant glut...