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

Journal Article (Journal Article)

RATIONALE: 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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • July 1, 2009

Published In

Volume / Issue

  • 180 / 1

Start / End Page

  • 11 - 18

PubMed ID

  • 19324975

Pubmed Central ID

  • PMC2701501

Electronic International Standard Serial Number (EISSN)

  • 1535-4970

Digital Object Identifier (DOI)

  • 10.1164/rccm.200807-1186OC


  • eng

Conference Location

  • United States