title: Impaired lung homeostasis in neonatal mice exposed to cigarette smoke.
abstract: In infants, smoke exposure is associated with more respiratory illnesses and decreased lung function. We hypothesized that perinatal lung is particularly susceptible to the damaging effects of cigarette smoke (CS) and that exposure to CS during this period may alter expression of immune response genes and adversely affect lung growth. To test this, we exposed neonatal mice to 14 days of CS. Immediately after exposure to CS, pulmonary gene expression profiling was performed on 2-week-old CS-exposed lung and age-matched control lung. Nitrotyrosine, TUNEL, MAC3, and phospho-SMAD-2 (p-SMAD2) staining was also performed. At 8 weeks of age, lung volume measurements were determined and mean linear intercept measurements were calculated. Pulmonary gene expression profiling revealed that CS exposure significantly inhibited type 1 and type 2 interferon pathway genes in neonatal lung, compared with age-matched control lung. Neonatal CS-exposed lung also had a significant increase in n-tyrosine, TUNEL, and p-SMAD2 staining when compared with adult CS-exposed lung and age-matched control lung. Lung volumes at 8 weeks of age were modestly but significantly decreased in mice exposed to CS in the neonatal period compared with age-matched controls, consistent with impaired lung growth. The results of this study indicate that exposure to CS during the neonatal period inhibits expression of genes involved in innate immunity and mildly impairs postnatal lung growth. These findings may in part explain the increased incidence of respiratory symptoms in infants and children exposed to CS.
authors.affiliation: Department of Pediatrics, Division of Pediatric Pulmonary, Johns Hopkins Hospital, Park 316/600 N. Wolfe St., Baltimore, MD 21287-2533, USA. smorrow@jhmi.edu
authors.forename: Sharon
authors.initials: S
authors.lastname: McGrath-Morrow
authors.forename: Tirumalai
authors.initials: T
authors.lastname: Rangasamy
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cho
authors.forename: Thomas
authors.initials: T
authors.lastname: Sussan
authors.forename: Enid
authors.initials: E
authors.lastname: Neptune
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007109:Immunity / Q000187:drug effects / Q000235:genetics; D019570:Inhalation Exposure; D007372:Interferons / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D012906:Smoke; D053781:Transforming Growth Factor beta2; D007372:Interferons; D020558:GTP Phosphohydrolases