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

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Abstract

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.

Original languageEnglish
Pages (from-to)L174-L183
Number of pages10
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Sirolimus
Glutamine
Lipopolysaccharides
Epithelial Cells
Lung
Phosphotransferases
Phosphorylation
Respiratory System
Transcriptional Activation
Cultured Cells
Cell Survival
Pneumonia
Air
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

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title = "Glutamine modulates lipopolysaccharide-induced activation of NF- kB via the AKt/mTOR pathway in lung epithelial cells",
abstract = "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.",
keywords = "BEAS-2B, Mammalian target of rapamycin, Nuclear factor- B, BEAS-2B, Mammalian target of rapamycin, Nuclear factor- kB",
author = "Yu-Chen Hou and Wan-Chun Chiu and Yeh, {Chiu Li} and Sung-Ling Yeh",
year = "2012",
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doi = "10.1152/ajplung.00066.2011",
language = "English",
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pages = "L174--L183",
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T1 - Glutamine modulates lipopolysaccharide-induced activation of NF- kB via the AKt/mTOR pathway in lung epithelial cells

AU - Hou, Yu-Chen

AU - Chiu, Wan-Chun

AU - Yeh, Chiu Li

AU - Yeh, Sung-Ling

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

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KW - Mammalian target of rapamycin

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KW - Nuclear factor- kB

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