title: PPARγ agonist rosiglitazone prevents perinatal nicotine exposure-induced asthma in rat offspring.
abstract: Perinatal exposure to maternal smoke is associated with adverse pulmonary effects, including reduced lung function and increased incidence of asthma. However, the mechanisms underlying these effects are unknown, and there is no effective preventive and/or therapeutic intervention. Recently, we suggested that downregulation of homeostatic mesenchymal peroxisome proliferator-activated receptor-γ (PPARγ) signaling following in utero nicotine exposure might contribute to chronic lung diseases such as asthma. We used an in vivo rat model to determine the effect of perinatal nicotine exposure on 1) offspring pulmonary function, 2) mesenchymal markers of airway contractility in trachea and lung tissue, and 3) whether administration of a PPARγ agonist, rosiglitazone (RGZ), blocks the molecular and functional effects of perinatal nicotine exposure on offspring lung. Pregnant Sprague-Dawley rat dams received placebo, nicotine, or nicotine + RGZ daily from embryonic day 6 until postnatal day 21, when respiratory system resistance, compliance, tracheal contractility, and the expression of markers of pulmonary contractility were determined. A significant increase in resistance and a decrease in compliance under basal conditions, with more pronounced changes following methacholine challenge, were observed with perinatal nicotine exposure compared with control. Tracheal constriction response and expression of mesenchymal markers of airway contractility were also significantly increased following perinatal nicotine exposure. Concomitant treatment with RGZ completely blocked the nicotine-induced alterations in pulmonary function, as well as the markers of airway contractility, at proximal and distal airway levels. These data suggest that perinatal smoke exposure-induced asthma can be effectively blocked by PPARγ agonists.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakurai
authors.forename: E M
authors.initials: EM
authors.lastname: O'Roark
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000517:prevention & control*; D005260:Female; D016210:Methacholine Chloride; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016210:Methacholine Chloride; D009538:Nicotine