Glutamine modulates lipopolysaccharide-induced activation of NF-κB via the Akt/mTOR pathway in lung epithelial cells
Glutamine modulates lipopolysaccharide-induced activation of NF-κB via the Akt/mTOR pathway in lung epithelial cells
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DOI：
10.1152/ajplung.00066.2011
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发表时间：
2012-01-01
影响因子：
4.9
通讯作者：
Yeh, Sung-Ling
中科院分区：
文献类型：
--
作者：
Hou, Yu-Chen;Chiu, Wan-Chun;Yeh, Sung-Ling
侯玉春，赵文武，叶春林，叶世林。谷氨酰胺通过Akt/mTOR通路调节脂多糖诱导的肺上皮细胞nf - κ B活化。[J] .中国生物医学工程学报，2016,31(2):444 - 444。首次发表于2011年10月14日；doi: 10.1152 / ajplung.00066.2011。肺上皮细胞是呼吸系统中重要的屏障，通过活化核因子(NF)- κ B引发炎症反应，阻止病原体侵入机体。脂多糖（LPS）是一种常见的病原体相关刺激物，可激活I κ B激酶（IKK），通过调节NF-kappa B的核易位和磷酸化来调节NF-kappa B介导的炎症。先前的研究表明，Akt和哺乳动物雷帕霉素靶蛋白（mTOR）参与IKK的磷酸化以激活NF-kappa B。研究表明，在BEAS-2B细胞中，谷氨酰胺（GLN）通过Akt/mTOR/IKK通路调节lps诱导的NF-kappa B活化。将深层培养的BEAS-2B细胞置于含有不同浓度GLN（0、0.5、1和2.5 mM）和1 kappa g/ml LPS的培养基中。结果表明，GLN剥夺诱导Akt/mTOR/IKK信号磷酸化，NF-kappa B核易位和NF-kappa B磷酸化水平升高，NF-kappa B依赖性转录活性上调，而这一活性被GLN抑制。补充GLN也可降低nf - κ b靶基因的表达。GLN可提高细胞活力，而0.5 mM GLN对Akt/mTOR/IKK/NF-kappa B信号级联的抑制程度更大。在气液界面条件下培养的细胞中，还观察到GLN对NF-kappa B活化的抑制作用。这些结果表明，GLN剥夺增加了lps诱导的NF-kappa B激活和转录活性，而GLN给予逆转了这一现象。这些发现提供了GLN调节lps诱导的肺上皮细胞nf - κ B活化的潜在机制，并暗示维持GLN的生理浓度对于预防lps诱导的肺部炎症至关重要。
Hou YC, Chiu WC, Yeh CL, Yeh SL. Glutamine modulates lipopolysaccharide-induced activation of NF-kappa B via the Akt/mTOR pathway in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 302: L174 -L183, 2012. First published October 14, 2011; doi: 10.1152/ajplung.00066.2011.-Lung epithelial cells are important barriers in the respiratory system that provoke inflammatory responses through nuclear factor (NF)-kappa B activation to prevent pathogens from invading the body. Lipopolysaccharide (LPS) is a common pathogen-associated stimulus that activates I kappa B kinase (IKK) to regulate NF-kappa B-mediated inflammation through modulating nuclear translocation and phosphorylation of NF-kappa B. Previously, it was shown that Akt and the mammalian target of rapamycin (mTOR) are involved in the phosphorylation of IKK to activate NF-kappa B. Herein, we demonstrate that glutamine (GLN) modulated LPS-induced activation of NF-kappa B 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 kappa g/ml LPS. Results showed that GLN deprivation induced phosphorylation of Akt/mTOR/IKK signaling, increased levels of NF-kappa B nuclear translocation and phosphorylated NF-kappa B, and upregulated NF-kappa B-dependent transcriptional activity, which was suppressed by GLN administration. Expressions of NF-kappa B-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-kappa B signaling cascade. The inhibitory effects of GLN on NF-kappa B activation were also observed in cells cultured under air-liquid interface condition. These results indicate that GLN deprivation increased LPS-induced NF-kappa B activation and transcriptional activity, which was reversed by GLN administration. The findings provide potential mechanisms of GLN's modulation of LPS-induced NF-kappa B activation in lung epithelial cells and imply that maintaining a physiological concentration of GLN is essential in preventing LPS-induced lung inflammation.