NOS2 regulation of LPS-induced airway inflammation via S-nitrosylation of NF-{kappa}B p65.


Journal Article

Inducible nitric oxide synthase (NOS2) expression is increased in the airway epithelium in acute inflammatory disorders although the physiological impact remains unclear. We have previously shown that NOS2 inhibits NF-κB (p50-p65) activation in respiratory epithelial cells by inducing S-nitrosylation of the p65 monomer (SNO-p65). In addition, we have demonstrated that mouse lung SNO-p65 levels are acutely depleted in a lipopolysaccharide (LPS) model of lung injury and that augmenting SNO-p65 levels before LPS treatment results in decreased airway epithelial NF-κB activation, airway inflammation, and lung injury. We now show that aerosolized LPS induces NOS2 expression in the respiratory epithelium concomitant with an increase in lung SNO-p65 levels and a decrease in airway NF-κB activity. Genetic deletion of NOS2 results in an absence of SNO-p65 formation, persistent NF-κB activity in the respiratory epithelium, and prolonged airway inflammation. These results indicate that a primary function of LPS-induced NOS2 expression in the respiratory epithelium is to modulate the inflammatory response through deactivation of NF-κB via S-nitrosylation of p65, thereby counteracting the initial stimulus-coupled denitrosylation.

Full Text

Duke Authors

Cited Authors

  • Kelleher, ZT; Potts, EN; Brahmajothi, MV; Foster, MW; Auten, RL; Foster, WM; Marshall, HE

Published Date

  • September 2011

Published In

Volume / Issue

  • 301 / 3

Start / End Page

  • L327 - L333

PubMed ID

  • 21724860

Pubmed Central ID

  • 21724860

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00463.2010


  • eng

Conference Location

  • United States