Data from: 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
glutathione, activation of NRF2, and induction of oxidative stress
responsive genes. Further, targeted antioxidant treatment of lung
fibroblasts partially mitigated the oxidative stress response gene
expression in adjacent human bronchial epithelial cells during diesel
exhaust particulate exposure. This indicates that exposure induced
oxidative stress in the airway extends beyond the bronchial epithelial
barrier and that lung fibroblasts are both a target and a mediator of the
adverse effects of inhaled chemical exposures despite a lack of direct
exposure to the inhaled material. These findings illustrate the value of
co-culture models and suggest that trans-epithelial exposure effects
should be considered in inhalation toxicology research and testing.