title: The lung response to ozone is determined by age and is partially dependent on toll-Like receptor 4.
abstract: BACKGROUND
  Ozone pollution has adverse effects on respiratory health in children and adults. This study was carried out in the mouse model to investigate the influence of age and to define the role of toll-like receptor four (TLR4) in the lung response to ozone exposure during postnatal development.
  
  
  METHODS
  Female mice (1 to 6 weeks of age) were exposed for 3 h to ozone (1 part per million) or filtered air. Analyses were carried out at six and 24 h after completion of exposure, to assess the effects on lung permeability, airway neutrophilia, expression of antioxidants and chemokines, and mucus production. The role of TLR4 was defined by examining TLR4 expression in the lung during development, and by investigating the response to ozone in tlr4-deficient mice.
  
  
  RESULTS
  Metallothionein-1, calcitonin gene-related product, and chemokine C-X-C ligand (CXCL) five were consistent markers induced by ozone throughout development. Compared with adults, neonates expressed lower levels of pulmonary TLR4 and responded with increased mucus production, and developed an attenuated response to ozone characterized by reduced albumin leakage and neutrophil influx into the airways, and lower expression of CXCL1 and CXCL2 chemokines. Examination of the responses in tlr4-deficient mice indicated that ozone-mediated airway neutrophilia, but not albumin leakage or mucus production were dependent on TLR4.
  
  
  CONCLUSIONS
  Collectively, the data demonstrate that the response to ozone is determined by age and is partially dependent on TLR4 signaling. The reduced responsiveness of the neonatal lung to ozone may be due at least in part to insufficient pulmonary TLR4 expression.
authors.affiliation: Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, 80206, CO, USA.
authors.forename: Kelsa
authors.initials: K
authors.lastname: Gabehart
authors.affiliation: Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, 80206, CO, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Correll
authors.affiliation: Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, 80206, CO, USA.|Current address: University of Colorado Denver, Children's Hospital, Aurora, CO, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Loader
authors.affiliation: Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, 80206, CO, USA.|Current address: University of Colorado Denver, Children's Hospital, Aurora, CO, USA.
authors.forename: Carl W
authors.initials: CW
authors.lastname: White
authors.affiliation: Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, 80206, CO, USA. DakhamaA@NJHealth.org.
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
mesh_terms: D000367:Age Factors; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D005260:Female; D019570:Inhalation Exposure; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D015415:Biomarkers; D018925:Chemokines; D009479:Neuropeptides; D012709:Serum Albumin; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D010126:Ozone