Gene expression profiling of LPS-stimulated murine macrophages and role of the NF-κB and PI3K/mTOR signaling pathways
Gene expression profiling of LPS-stimulated murine macrophages and role of the NF-κB and PI3K/mTOR signaling pathways
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DOI：
10.1196/annals.1397.071
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Raes, M.
中科院分区：
文献类型：
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作者：
Dos Santos, S.;Delattre, A.-I.;Raes, M.
脂多糖（LPS）是革兰氏阴性菌外膜的主要成分，激活免疫细胞中的广谱信号通路。在这篇文章中，在存在或不存在NF-κ B通路（BAY 11-7082）和PI 3 K通路（LY 294002）的特异性抑制剂的情况下，用1 μ g/mL LPS刺激RAW 264.7细胞4小时。使用DNA微阵列“双芯片小鼠炎症”表征基因表达谱。“这个阵列监测了233个编码蛋白质的基因的表达，这些蛋白质在炎症中起作用。这两种信号通路在对LPS的应答中发挥重要作用，但它们并不完全重叠。例如，编码PAF受体、PAT-1、PIA 2（V组）、IL-13受体（α 2）和GTP环化水解酶1的基因在LPS处理后上调，但这种上调被LY 294002抵消。对于BAY 11-7082观察到相同的结果：编码试剂盒配体、TLR 2或TNFRSF 5的基因主要受NF-κ B控制。NF-κ B在巨噬细胞对LPS的反应中起着重要的作用，但我们也发现PI 3 K通路部分参与其中。进一步的mTOR特异性抑制剂（雷帕霉素）实验将提供更多关于PI 3 K/mTOR通路在LPS刺激的巨噬细胞炎症反应中的特异性贡献的信息。
Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, activates a broad spectrum of signaling pathways in immune cells. In this article, RAW264.7 cells have been stimulated for 4 h with 1 mu g/mL of LPS in the presence or not of specific inhibitors of the NF-kappa B pathway (BAY 11-7082) and the PI3K pathway (LY294002). Gene expression profiles were characterized using the DNA microarray "Dual Chip Mouse Inflammation." This array monitors the expression of 233 genes encoding proteins playing a role in inflammation. Both signaling pathways exert an important role in the response to LPS, but they are not completely overlapping. For example, genes encoding the PAF receptor, PAT-1, PIA2 (group V), IL-13 receptor (alpha 2), and GTP cyclohydrolase 1, were upregulated after LPS treatment, but this upregulation was counteracted by LY294002. The same was observed for BAY 11-7082 : genes encoding the kit ligand, TLR2, or TNFRSF5 were mainly under the control of NF-KB. NF-KB plays an important role in the macrophage response to LPS, but we have also shown that the PI3K pathway partially contributes to it. Further experiments with the specific inhibitor of mTOR (rapamycin) will provide more information on the specific contribution of the PI3K/mTOR pathway in the inflammatory response in LPS-stimulated macrophages.