title: Polycyclic aromatic hydrocarbons impair function of β2-adrenergic receptors in airway epithelial and smooth muscle cells.
abstract: Incomplete combustion produces a pollutant mixture that includes polycyclic aromatic hydrocarbons (PAHs). Previous work by the Columbia Center for Children's Environmental Health (CCCEH) and others linked exposure to PAH with symptoms of asthma and other adverse health effects in young children. Inhaled β(2)-adrenergic agonists are mainstays in the treatment of reactive airway diseases. These exogenous catecholamines engage membrane-bound β(2)-adrenergic receptors (β(2)AR) on airway epithelial and smooth muscle cells to cause airway dilation. We hypothesized that exposure to PAH might similarly interfere with the function of β(2)AR in airway epithelial or smooth muscle cells, reducing the efficacy of a medication important for the treatment of asthma symptoms. A PAH mixture was devised, based on ambient levels measured prenatally among a cohort of pregnant women participating at the CCCEH. Primary airway epithelial and smooth muscle cells were exposed to varying concentrations of the PAH mixture, and expression, function, and signaling of β(2)AR were assessed. Murine tracheal epithelial cells and human airway smooth muscle cells, after exposure to a PAH mixture, exhibited reduced expression and function of β(2)AR. These findings support our hypothesis that environmentally relevant PAHs can impede β(2)AR-mediated airway relaxation, and suggest a new paradigm where air pollutants not only contribute to the pathogenesis of childhood asthma, but also diminish responsiveness to standard therapy.
authors: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Hospital, New York, NY 10003, USA. pfactor@chpnet.org
authors: Phillip
authors: P
authors: Factor
authors: Alexander T
authors: AT
authors: Akhmedov
authors: Jacob D
authors: JD
authors: McDonald
authors: Anna
authors: A
authors: Qu
authors: Jie
authors: J
authors: Wu
authors: Hong
authors: H
authors: Jiang
authors: Trisha
authors: T
authors: Dasgupta
authors: Reynold A
authors: RA
authors: Panettieri
authors: Frederica
authors: F
authors: Perera
authors: Rachel L
authors: RL
authors: Miller
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