NOS2 regulation of LPS-induced airway inflammation via S-nitrosylation of NF-κB p65
NOS2 regulation of LPS-induced airway inflammation via S-nitrosylation of NF-κB p65
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DOI：
10.1152/ajplung.00463.2010
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发表时间：
2011-09-01
影响因子：
4.9
通讯作者：
Marshall, Harvey E.
中科院分区：
文献类型：
--
作者：
Kelleher, Zachary T.;Potts, Erin N.;Marshall, Harvey E.
Kelleher ZT, Potts EN, brahmajthi MV, Foster MW, Auten RL, Foster WM, Marshall HE。NOS2通过NF-kappa bp65的s -亚硝基化调控lps诱导的气道炎症。[J] .中国生物医学工程学报，2011,31(2):327- 331。首次发表于2011年7月1日；doi: 10.1152 / ajplung.00463.2010。诱导型一氧化氮合酶（NOS2）在急性炎症性疾病的气道上皮中表达增加，但其生理影响尚不清楚。我们之前已经证明，NOS2通过诱导p65单体（SNO-p65）的s -亚硝基化抑制呼吸上皮细胞中NF-kappa B （p50-p65）的激活。此外，我们已经证明，在脂多糖（LPS）肺损伤模型中，小鼠肺SNO-p65水平急剧减少，并且在LPS治疗前增加SNO-p65水平导致气道上皮nf - κ B激活减少，气道炎症和肺损伤。我们现在表明，雾化LPS诱导呼吸道上皮中NOS2表达，同时肺SNO-p65水平升高，气道nf - κ B活性降低。NOS2基因缺失导致SNO-p65形成缺失，呼吸上皮内NF-kappa B活性持续，气道炎症延长。这些结果表明，lps诱导的呼吸上皮中NOS2表达的主要功能是通过p65的s-亚硝基化使NF-kappa B失活来调节炎症反应，从而抵消最初刺激偶联的脱硝基化。
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.