Inflammatory and repair pathways induced in human bronchoalveolar lavage cells with ozone inhalation

PLoS One. 2015 Jun 2;10(6):e0127283. doi: 10.1371/journal.pone.0127283. eCollection 2015.


Background: Inhalation of ambient levels of ozone causes airway inflammation and epithelial injury.

Methods: To examine the responses of airway cells to ozone-induced oxidative injury, 19 subjects (7 with asthma) were exposed to clean air (0ppb), medium (100ppb), and high (200ppb) ambient levels of ozone for 4h on three separate occasions in a climate-controlled chamber followed by bronchoscopy with bronchoalveolar lavage (BAL) 24h later. BAL cell mRNA expression was examined using Affymetrix GeneChip Microarray. The role of a differentially expressed gene (DEG) in epithelial injury was evaluated in an in vitro model of injury [16HBE14o- cell line scratch assay].

Results: Ozone exposure caused a dose-dependent up-regulation of several biologic pathways involved in inflammation and repair including chemokine and cytokine secretion, activity, and receptor binding; metalloproteinase and endopeptidase activity; adhesion, locomotion, and migration; and cell growth and tumorigenesis regulation. Asthmatic subjects had 1.7- to 3.8-fold higher expression of many DEGs suggestive of increased proinflammatory and matrix degradation and remodeling signals. The most highly up-regulated gene was osteopontin, the protein level of which in BAL fluid increased in a dose-dependent manner after ozone exposure. Asthmatic subjects had a disproportionate increase in non-polymerized osteopontin with increasing exposure to ozone. Treatment with polymeric, but not monomeric, osteopontin enhanced the migration of epithelial cells and wound closure in an α9β1 integrin-dependent manner.

Conclusions: Expression profiling of BAL cells after ozone exposure reveals potential regulatory genes and pathways activated by oxidative stress. One DEG, osteopontin, promotes epithelial wound healing in an in vitro model of injury.

Publication types

  • Clinical Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Air Conditioning
  • Asthma / physiopathology*
  • Bronchoalveolar Lavage Fluid / cytology*
  • Bronchoscopy
  • Cell Line / drug effects
  • Cell Movement / drug effects
  • Cluster Analysis
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / genetics
  • Inflammation / pathology
  • Male
  • Osteopontin / genetics*
  • Osteopontin / metabolism
  • Osteopontin / pharmacology
  • Oxidative Stress / drug effects
  • Ozone / administration & dosage
  • Ozone / adverse effects*


  • Osteopontin
  • Ozone

Associated data

  • GEO/GSE58682