Postnatal exposure history and airways: Oxidant stress responses in airway explants

Shannon R. Murphy, Edward S Schelegle, Patricia C. Edwards, Lisa Miller, Dallas M. Hyde, Laura S. Van Winkle

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Postnatally, the lung continues to grow and differentiate while interacting with the environment. Exposure to ozone (O3) and allergens during postnatal lung development alters structural elements of conducting airways, including innervation and neurokinin abundance. These changes have been linked with development of asthma in a rhesus monkey model. We hypothesized that O 3 exposure resets the ability of the airways to respond to oxidant stress and that this is mediated by changes in the neurokinin-1 receptor (NK-1R). Infant rhesus monkeys received episodic exposure to O3 biweekly with or without house dust mite antigen (HDMA) from 6 to 12 months of age. Age-matched monkeys were exposed to filtered air (FA). Microdissected airway explants from midlevel airways (intrapulmonary generations 5-8) for four to six animals in each of four groups (FA, O3, HDMA, and HDMA+O 3) were tested for NK-1R gene responses to acute oxidant stress using exposure to hydrogen peroxide (1.2 mM), a lipid ozonide (10 μM), or sham treatment for 4 hours in vitro. Airway responses were measured using real-time quantitative RT-PCR of NK-1R and IL-8 gene expression. Basal NK-1R gene expression levels were not different between the exposure groups. Treatment with ozonide or hydrogen peroxide did not change NK-1R gene expression in animals exposed to FA, HDMA, or HDMA+O3. However, treatment in vitro with lipid ozonide significantly increased NK-1R gene expression in explants from O3-exposed animals. We conclude that a history of prior O3 exposure resets the steady state of the airways to increase the NK-1R response to subsequent acute oxidant stresses.

Original languageEnglish (US)
Pages (from-to)815-823
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume47
Issue number6
DOIs
StatePublished - Dec 2012

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Keywords

  • Bronchial epithelium
  • Lung
  • Nur77
  • Substance P

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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