title: Protection from lipopolysaccharide-induced lung injury by augmentation of airway S-nitrosothiols.
abstract: BACKGROUND
  S-Nitrosothiols (SNO) inhibit immune activation of the respiratory epithelium and airway SNO levels are decreased in inflammatory lung disease. Ethyl nitrite (ENO) is a gas with chemical properties favoring SNO formation. Augmentation of airway SNO by inhaled ENO treatment may decrease lung inflammation and subsequent injury by inhibiting activation of the airway epithelium.
  
  
  OBJECTIVE
  To determine the effect of inhaled ENO on airway SNO levels and LPS-induced lung inflammation/injury.
  
  
  METHODS
  Mice were treated overnight with inhaled ENO (10 ppm) or air, followed immediately by exposure to aerosolized LPS or saline. Parameters of inflammation and lung injury were quantified 1 hour after completion of the aerosol exposure and correlated to lung airway and tissue SNO levels.
  
  
  RESULTS
  Aerosolized LPS induced a decrease in airway and lung tissue SNO levels including S-nitrosylated NF-kappaB. The decrease in lung SNO was associated with an increase in lung NF-kappaB activity, cytokine/chemokine expression (keratinocyte-derived chemokine, tumor necrosis factor-alpha, and IL-6), airway neutrophil influx, and worsened lung compliance. Pretreatment with inhaled ENO restored airway SNO levels and reduced LPS-mediated NF-kappaB activation thereby inhibiting the downstream inflammatory response and preserving lung compliance.
  
  
  CONCLUSIONS
  Airway SNO serves an antiinflammatory role in the lung. Inhaled ENO can be used to augment airway SNO and protect from LPS-induced acute lung injury.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. marsh015@mc.duke.edu
authors.forename: Harvey E
authors.initials: HE
authors.lastname: Marshall
authors.forename: Erin N
authors.initials: EN
authors.lastname: Potts
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Kelleher
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Stamler
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Richard L
authors.initials: RL
authors.lastname: Auten