lung lymph

lung

acute lung

fetal lung

cigarette smoke

lung growth

surfactant protein

bal fluid

ozone exposure

The FASEB Journal

Ozone is a ubiquitous urban air pollutant that causes airway inflammation and hyperresponsiveness. Evidence indicates that alterations in lung lipid homeostasis due to dysregulated catabolism by alveolar macrophages and/or disrupted recycling by alveolar epithelial type II cells drives inflammation and chronic lung injury. RNA‐seq analysis of alveolar macrophages revealed that exposure of mice to ozone resulted in alterations in inflammatory and lipid metabolism pathways, and down‐regulation of PPARγ, a nuclear transcription factor important in controlling lipid metabolism, macrophage activation, and inflammation resolution. In the present studies, we analyzed the role of PPARγ in ozone‐induced alterations in lung lipid homeostasis. Female C57BL/6J mice were treated with the PPARγ agonist, rosiglitazone or vehicle control by daily intraperitoneal injection beginning 24 hr prior to exposure to ozone (0.8 ppm, 3 hr) or air; mice were euthanized 72 hr post ozone. Bronchoalveolar lavage fluid (BAL) was collected and analyzed for total protein and phospholipid content, and expression of surfactant proteins. Effects on pulmonary function were assessed using a SciReq Flexivent. Ozone exposure resulted in increases in total protein and phospholipid content in BAL, consistent with lung injury and dysregulation of lipid metabolism. An increase in levels of the hydrophilic collectin, surfactant protein D (SP‐D) and a decrease in the hydrophobic surfactant protein B (SP‐B) were also observed in BAL after ozone exposure. SP‐B and phospholipids regulate pulmonary function by maintaining lung surface tension and hysteresivity. Ozone exposure reduced lung hysteresivity at positive end‐expiratory pressures of 1 and 3 cm H 2 0 indicating reduced viscoelasticity of the lungs. Rosiglitazone administration significantly reduced BAL phospholipid content and restored SP‐B to control levels. Consistent with these findings, rosiglitazone rescued ozone‐induced impairment of lung function. Collectively, these results suggest that ozone exp...

Rosiglitazone restores pulmonary surfactant and lipid homeostasis in mice exposed to ozone