4.5 Article

Transcriptional Profiling of the Murine Airway Response to Acute Ozone Exposure

Journal

TOXICOLOGICAL SCIENCES
Volume 173, Issue 1, Pages 114-130

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfz219

Keywords

ozone; air pollution; transcriptomics; lung; inflammation; injury; mouse

Categories

Funding

  1. National Institute of Environmental Health Sciences of the National Institute of Health [ES024965, ES024965-S1, P30ES010126]
  2. Albert C. and Lois E. Dehn Endowment at Michigan State University for Veterinary Medicine (Pathobiology and Diagnostic Investigation)

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Ambient ozone (O-3) exposure has serious consequences on respiratory health, including airway inflammation and injury. Decades of research have yielded thorough descriptions of these outcomes; however, less is known about the molecular processes that drive them. The aim of this study was to further describe the cellular and molecular responses to O-3 exposure in murine airways, with a particular focus on transcriptional responses in 2 critical pulmonary tissue compartments: conducting airways (CA) and airway macrophages (AM). After exposing adult, female C57BL/6J mice to filtered air, 1 or 2ppm O-3, we assessed hallmark responses including airway inflammation (cell counts and cytokine secretion) and injury (epithelial permeability), followed by gene expression profiling of CA and AM by RNA-seq. As expected, we observed concentration-dependent increases in airway inflammation and injury. Conducting airways and AM both exhibited changes in gene expression to both 1 and 2ppm O-3 that were largely compartment-specific. In CA, genes associated with epithelial barrier function, detoxification processes, and cellular proliferation were altered, while O-3 affected genes involved in innate immune signaling, cytokine production, and extracellular matrix remodeling in AM. Further, CA and AM also exhibited notable differences in concentration-response expression patterns for large numbers of genes. Overall, our study has described transcriptional responses to acute O-3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O-3 and in 2 important O-3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O-3 toxicity, and reveal a variety of targets for focused follow-up studies.

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