Protection from lipopolysaccharide-induced lung injury by augmentation of airway S-nitrosothiols.


Journal Article

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.To determine the effect of inhaled ENO on airway SNO levels and LPS-induced lung inflammation/injury.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.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.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.

Full Text

Duke Authors

Cited Authors

  • Marshall, HE; Potts, EN; Kelleher, ZT; Stamler, JS; Foster, WM; Auten, RL

Published Date

  • July 2009

Published In

Volume / Issue

  • 180 / 1

Start / End Page

  • 11 - 18

PubMed ID

  • 19324975

Pubmed Central ID

  • 19324975

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/rccm.200807-1186OC


  • eng