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

作者：Kelleher Zachary T; Potts Erin N; Brahmajothi Mulugu V; Foster Matthew W; Auten Richard L; Foster W Michael; Marshall Harvey E^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2011, 301(3): L327-L333.

DOI：10.1152/ajplung.00463.2010

• S-nitrosothiol
• nitric oxide synthase
• nuclear factor-kappa B
• acute lung injury

Kelleher ZT, Potts EN, Brahmajothi MV, Foster MW, Auten RL, Foster WM, Marshall HE. NOS2 regulation of LPS-induced airway inflammation via S-nitrosylation of NF-kappa B p65. Am J Physiol Lung Cell Mol Physiol 301: L327-L333, 2011. First published July 1, 2011; doi:10.1152/ajplung.00463.2010.-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-kappa B (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-kappa B 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-kappa B activity. Genetic deletion of NOS2 results in an absence of SNO-p65 formation, persistent NF-kappa B 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-kappa B via S-nitrosylation of p65, thereby counteracting the initial stimulus-coupled denitrosylation.

• 出版日期2011-9