Transcriptional Profiling of the Murine Airway Response to Acute Ozone Exposure

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.