Prenatal and Postnatal Polycyclic Aromatic Hydrocarbon Exposure, Airway Hyperreactivity, and Beta-2 Adrenergic Receptor Function in Sensitized Mouse Offspring

Despite data associating exposure to traffic-related polycyclic aromatic hydrocarbons (PAH) in asthma, mechanistic support has been limited. We hypothesized that both prenatal and early postnatal exposure to PAH would increase airway hyperreactivity (AHR) and that the resulting AHR may be insensitive to treatment with a β (2)AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered β (2)AR gene expression and DNA methylation in mouse lungs. Mice were exposed prenatally or postnatally to a nebulized PAH mixture versus negative control aerosol 5 days a week. Double knockout β (2)AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced β (2)AR gene expression among nonsensitized mice offspring, but not increases in DNA methylation or AHR. Postnatal exposure to PAH was borderline associated with increased AHR among sensitized wildtype, but not knockout mice. In the first study that delivers PAH aerosols to mice in a relatively physiological manner, small effects on AHR and β (2)AR gene expression, but not β (2)AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects β (2)AR function, although the impact on the efficacy of β (2)AR agonist drugs used in treating asthma remains uncertain.