title: Glutamine modulates lipopolysaccharide-induced activation of NF-κB 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)-κB activation to prevent pathogens from invading the body. Lipopolysaccharide (LPS) is a common pathogen-associated stimulus that activates IκB kinase (IKK) to regulate NF-κB-mediated inflammation through modulating nuclear translocation and phosphorylation of NF-κB. Previously, it was shown that Akt and the mammalian target of rapamycin (mTOR) are involved in the phosphorylation of IKK to activate NF-κB. Herein, we demonstrate that glutamine (GLN) modulated LPS-induced activation of NF-κB 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 μg/ml LPS. Results showed that GLN deprivation induced phosphorylation of Akt/mTOR/IKK signaling, increased levels of NF-κB nuclear translocation and phosphorylated NF-κB, and upregulated NF-κB-dependent transcriptional activity, which was suppressed by GLN administration. Expressions of NF-κB-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-κB signaling cascade. The inhibitory effects of GLN on NF-κB activation were also observed in cells cultured under air-liquid interface condition. These results indicate that GLN deprivation increased LPS-induced NF-κB activation and transcriptional activity, which was reversed by GLN administration. The findings provide potential mechanisms of GLN's modulation of LPS-induced NF-κB activation in lung epithelial cells and imply that maintaining a physiological concentration of GLN is essential in preventing LPS-induced lung inflammation.
authors: School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.
authors: Yu-Chen
authors: YC
authors: Hou
authors: Wan-Chun
authors: WC
authors: Chiu
authors: Chiu-Li
authors: CL
authors: Yeh
authors: Sung-Ling
authors: SL
authors: Yeh
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005973:Glutamine / Q000008:administration & dosage / Q000172:deficiency; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D005973:Glutamine; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051550:I-kappa B Kinase