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 2AR agonist drug, procaterol. Further, we hypothesized that these exposures would be associated with altered β 2AR 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 2AR mice were exposed postnatally only. Prenatal exposure to PAH was associated with reduced β 2AR 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 2AR gene expression, but not β 2AR agonist drug activity, were observed. If confirmed, the results may suggest that exposure to PAH, common ambient urban pollutants, affects β 2AR function, although the impact on the efficacy of β 2AR agonist drugs used in treating asthma remains uncertain.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, PH8E-101B, 630 W. 168th Street, New York, NY 10032, USA.
Sophie
S
Chu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, PH8E-101B, 630 W. 168th Street, New York, NY 10032, USA.
Hanjie
H
Zhang
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, PH8E-101B, 630 W. 168th Street, New York, NY 10032, USA.
Christina
C
Maher
Department of Toxicology, Lovelace Respiratory Research Institute, Albuquerque, NM 87101, USA.
Jacob D
JD
McDonald
Department of Environmental Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45201, USA.
Xiang
X
Zhang
Department of Environmental Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH 45201, USA.
Shuk-Mei
SM
Ho
Lamont-Doherty Earth Observatory, Columbia University, Palisades, NY 10964, USA.
Beizhan
B
Yan
Lamont-Doherty Earth Observatory, Columbia University, Palisades, NY 10964, USA.
Steven
S
Chillrud
Department of Environmental Health, Columbia University Mailman School of Public Health, New York, NY 10032, USA.
Frederica
F
Perera
Department of Medicine, University of Arizona, Tucson, AZ, 85721, USA.
Phillip
P
Factor
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, PH8E-101B, 630 W. 168th Street, New York, NY 10032, USA ; Department of Environmental Health, Columbia University Mailman School of Public Health, New York, NY 10032, USA ; Division of Pediatric Allergy and Immunology, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Rachel L
RL
Miller