Glutamine modulates lipopolysaccharide-induced activation of NF- kB via the AKt/mTOR pathway in lung epithelial cells

研究成果: 雜誌貢獻文章同行評審

32 引文 斯高帕斯(Scopus)

摘要

Lung epithelial cells are important barriers in the respiratory system that provoke inflammatory responses through nuclear factor (NF)-kB activation to prevent pathogens from invading the body. Lipopolysaccharide (LPS) is a common pathogen-associated stimulus that activates IkB kinase (IKK) to regulate NF- kB-mediated inflammation through modulating nuclear translocation and phosphorylation of NF- kB. Previously, it was shown that Akt and the mammalian target of rapamycin (mTOR) are involved in the phosphorylation of IKK to activate NF- kB. Herein, we demonstrate that glutamine (GLN) modulated LPS-induced activation of NF- kB through the Akt/mTOR/IKK pathway in BEAS-2B cells. BEAS-2B cells in submerged culture were placed in medium containing different concentrations of GLN (0, 0.5, 1, and 2.5 mM) with 1 kg/ml LPS. Results showed that GLN deprivation induced phosphorylation of Akt/mTOR/IKK signaling, increased levels of NF- kB nuclear translocation and phosphorylated NF- kB, and upregulated NF- kB-dependent transcriptional activity, which was suppressed by GLN administration. Expressions of NF- kB-targeted genes were also reduced by supplemental GLN. GLN administration improved cell viability, whereas 0.5 mM GLN had a greater extent of inhibition on the Akt/mTOR/IKK/NF- kB signaling cascade. The inhibitory effects of GLN on NF- kB activation were also observed in cells cultured under air-liquid interface condition. These results indicate that GLN deprivation increased LPS-induced NF- kB activation and transcriptional activity, which was reversed by GLN administration. The findings provide potential mechanisms of GLN's modulation of LPSinduced NF- kB activation in lung epithelial cells and imply that maintaining a physiological concentration of GLN is essential in preventing LPS-induced lung inflammation.
原文英語
頁(從 - 到)L174-L183
頁數10
期刊American Journal of Physiology - Lung Cellular and Molecular Physiology
302
發行號1
DOIs
出版狀態已發佈 - 一月 2012

Keywords

  • BEAS-2B
  • Mammalian target of rapamycin
  • Nuclear factor- kB

ASJC Scopus subject areas

  • 肺和呼吸系統醫學
  • 生理學(醫學)
  • 細胞生物學
  • 生理學

指紋

深入研究「Glutamine modulates lipopolysaccharide-induced activation of NF- <sub>k</sub>B via the AKt/mTOR pathway in lung epithelial cells」主題。共同形成了獨特的指紋。

引用此