%0 Journal Article
%T Prenatal and Postnatal Polycyclic Aromatic Hydrocarbon Exposure, Airway Hyperreactivity, and Beta-2 Adrenergic Receptor Function in Sensitized Mouse Offspring
%A Sophie Chu
%A Hanjie Zhang
%A Christina Maher
%A Jacob D. McDonald
%A Xiang Zhang
%A Shuk-Mei Ho
%A Beizhan Yan
%A Steven Chillrud
%A Frederica Perera
%A Phillip Factor
%A Rachel L. Miller
%J Journal of Toxicology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/603581
%X 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 ¦Â2AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered ¦Â2AR 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 ¦Â2AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced ¦Â2AR 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 ¦Â2AR gene expression, but not ¦Â2AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects ¦Â2AR function, although the impact on the efficacy of ¦Â2AR agonist drugs used in treating asthma remains uncertain. 1. Introduction Exposure to traffic-related air pollution has been associated with exacerbations of respiratory symptoms, decreased lung function, and the development of asthma [1¨C5]. Incomplete combustion of diesel exhaust particles emitted by motor vehicle engines produces a complex mixture of pollutants that includes significant concentrations of polycyclic aromatic hydrocarbons (PAH). Previously, our group at the Columbia Center for Children¡¯s Environmental Health (CCCEH) and others have shown that exposure to PAH was associated with asthma in children [1, 4, 6, 7]. Notably, the prenatal time window of exposure to PAH has been implicated in the development of childhood asthma, particularly in the presence of exposure to secondhand smoke [4, 8]. Also, repeated prenatal and early childhood exposure to pyrene, the predominant PAH in the NYC CCCEH local environment, has been associated with asthma regardless of exposure to secondhand smoke or seroatopy in the CCCEH cohort [1]. Despite the emergence of data associating exposure of PAH to asthma-related outcomes, mechanistic support has been limited. Inhaled ¦Â2-adrenergic agonists are common treatments for reactive airway diseases and used for short-term and long-term alleviation of
%U http://www.hindawi.com/journals/jt/2013/603581/