Metformin Inhibits Chemokine Expression Through the AMPK/NF-kappa B Signaling Pathway
Metformin Inhibits Chemokine Expression Through the AMPK/NF-kappa B Signaling Pathway
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二甲双胍通过 AMPK/NF-kappa B 信号通路抑制趋化因子表达
DOI：
10.1089/jir.2018.0061
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发表时间：
2018
影响因子：
2.3
通讯作者：
Ying Ying
中科院分区：
文献类型：
--
作者：
Ye Jinhui;Zhu Na;Sun Ruipu;Liao Wangdi;Fan Shipan;Shi Fuli;Lin Hui;Jiang Shuping;Ying Ying
炎症是由细胞因子和趋化因子介导的，它们被认为是炎症性疾病的靶标。越来越多的证据证明二甲双胍具有抗炎作用。然而，其根本机制尚未完全了解。在本研究中，我们旨在以小鼠巨噬细胞系RAW264.7细胞为模型，阐明二甲双胍对趋化因子表达的调节作用及其可能的机制。首先，我们用脂多糖（LPS）处理细胞，发现CXCL10和CXCL11的表达以剂量和时间依赖性方式被显着诱导，同时抑制AMPK活性。然后，我们用二甲双胍处理细胞，并通过实时定量聚合酶链反应（PCR）分析CCL2、CXCL10和CXCL11的表达。我们观察到二甲双胍阻止了 LPS 对这些趋化因子以及 IL-1 和 IL-6 的刺激作用。其次，二甲双胍对 LPS 诱导的趋化因子表达的抑制作用被化合物 C（AMPK 的化学抑制剂）减弱。最后，我们研究了在此情况下 NF-κB 信号通路是否受到二甲双胍的调节。我们的结果表明，二甲双胍抑制 I-κBα 和 p65 的磷酸化，同时激活 AMPK。因此，结果表明二甲双胍通过 AMPK 和 NF-κB 信号通路抑制 LPS 诱导的趋化因子表达。
Inflammation is mediated by cytokines and chemokines, which are considered targets of inflammatory diseases. Mounting evidence has demonstrated the anti-inflammatory benefits of metformin. However, the underlying mechanisms are not completely understood. In this study, we aim to elucidate the regulatory effects of metformin on chemokine expression and the possible mechanisms using RAW264.7 cells, a mouse macrophage cell line, as a model. First, we treated the cells with lipopolysaccharide (LPS), and found that the expression of CXCL10 and CXCL11 was markedly induced in a dose- and time-dependent fashion concurrent with the inhibition of AMPK activity. Then, we treated the cells with metformin, and analyzed the expression of CCL2, CXCL10, and CXCL11 by quantitative real-time polymerase chain reaction (PCR). We observed that metformin prevented the stimulating effect of LPS on these chemokines as well as IL-1 and IL-6. Second, the inhibitory effects of metformin on LPS-induced chemokine expression were diminished by Compound C, a chemical inhibitor of AMPK. Finally, we investigated whether the NF-κB signaling pathway is regulated by metformin in this setting. Our results showed that metformin inhibited the phosphorylation of I-κBα and p65 while it activated AMPK. Therefore, the results suggest that metformin inhibits LPS-induced chemokine expression through the AMPK and NF-κB signaling pathways.