Adenoviral E1A modulates inflammatory mediator expression by lung epithelial cells exposed to PM10

We examined the hypothesis that ambient particulate matter with a diameter of <10 mu m (PM10)-induced lung inflammation is amplified by latent adenovirus infection. Inflammatory mediator expression in response to PM10 exposure was compared between adenovirus E1A-transfected A549 alveolar epithelial cells and cells transfected with control plasmid. Messenger RNA was measured by the RNase protection assay and protein by ELISA or immunocytochemistry. Intercellular adhesion molecule-1 and IL-8 mRNA and protein were increased in E1A-positive cells exposed to 500 mu g/ml PM10. Monocyte chemoattractant protein-1 mRNA and protein were unchanged in E1A-positive cells but increased in E1A-negative cells after 100 and 500 mu g/ml PM10 exposure. Electrophoretic mobility shift assays showed increased NF-kappa B and decreased specificity protein 1 nuclear binding in E1A-positive cells exposed to PM10. These results indicate that E1A modulates cytokine and adhesion molecule expression in epithelial cells in a manner that could amplify PM10-induced lung inflammation. We suggest that this amplified inflammatory response may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease associated with exposure to particulate matter air pollution.