Sodium salicylate modulates inflammatory responses through AMP-activated protein kinase activation in LPS-stimulated THP-1 cells.
Sodium salicylate modulates inflammatory responses through AMP-activated protein kinase activation in LPS-stimulated THP-1 cells.
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水杨酸钠通过 LPS 刺激的 THP-1 细胞中 AMP 激活的蛋白激酶激活调节炎症反应
DOI：
10.1002/jcb.26249
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发表时间：
2018-01
影响因子：
4
通讯作者：
Mei W
中科院分区：
文献类型：
--
作者：
Bao W;Luo Y;Wang D;Li J;Wu X;Mei W
水杨酸钠（NaSal）是一种非甾体抗炎药。 NaSal 药理作用的推定机制包括抑制环氧合酶、血小板衍生的血栓素 A2 和 NF-κB 信号传导。最近的研究表明，水杨酸盐可以激活 AMP 激活蛋白激酶 (AMPK)，这是一种维持 ATP 产生和消耗之间平衡的能量传感器。据报道，AMPK 的抗炎作用是通过促进线粒体生物发生和脂肪酸氧化来介导的。然而，通过 AMPK 导致水杨酸盐介导的炎症的确切信号尚不清楚。在当前的研究中，我们研究了 NaSal 对 THP-1 单核细胞对脂多糖 (LPS) 攻击的炎症样反应的潜在影响。在存在或不存在 5mM NaSal 的情况下，使用或不使用 10ug/mL LPS 刺激 THP-1 细胞 24 小时。通过使用膜联蛋白 V/PI 染色的流式细胞术和 Bcl-2 抗凋亡蛋白的蛋白质印迹法来测量细胞凋亡。通过 EdU 掺入和增殖细胞核抗原 (PCNA) 的蛋白质印迹分析来检测细胞增殖。通过酶联免疫吸附测定（ELISA）测定促炎细胞因子（TNF-α、IL-1β、IL-6）的分泌。我们观察到 NaSal 激活 AMPK 伴随着诱导细胞凋亡、抑制细胞增殖以及增加 TNF-α 和 IL-1β 的分泌。这些效应可被 AMPK 抑制剂化合物 C 逆转。此外，NaSal/AMPK 激活抑制了 LPS 诱导的 STAT3 磷酸化，而复合 C 处理可逆转这种磷酸化。我们得出结论，AMPK 激活通过诱导细胞凋亡、减少细胞增殖、抑制 STAT3 活性以及产生 TNF-α 和 IL-1β，对 NaSal 介导的炎症很重要。
Sodium salicylate (NaSal) is a nonsteroidal anti‐inflammatory drug. The putative mechanisms for NaSal's pharmacologic actions include the inhibition of cyclooxygenases, platelet‐derived thromboxane A2, and NF‐κB signaling. Recent studies demonstrated that salicylate could activate AMP‐activated protein kinase (AMPK), an energy sensor that maintains the balance between ATP production and consumption. The anti‐inflammatory action of AMPK has been reported to be mediated by promoting mitochondrial biogenesis and fatty acid oxidation. However, the exact signals responsible for salicylate‐mediated inflammation through AMPK are not well‐understood. In the current study, we examined the potential effects of NaSal on inflammation‐like responses of THP‐1 monocytes to lipopolysaccharide (LPS) challenge. THP‐1 cells were stimulated with or without 10 ug/mL LPS for 24 h in the presence or absence of 5 mM NaSal. Apoptosis was measured by flow cytometry using Annexin V/PI staining and by Western blotting for the Bcl‐2 anti‐apoptotic protein. Cell proliferation was detected by EdU incorporation and by Western blot analysis for proliferating cell nuclear antigen (PCNA). Secretion of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) was determined by enzyme‐linked immunosorbent assay (ELISA). We observed that the activation of AMPK by NaSal was accompanied by induction of apoptosis, inhibition of cell proliferation, and increasing secretion of TNF‐α and IL‐1β. These effects were reversed by Compound C, an inhibitor of AMPK. In addition, NaSal/AMPK activation inhibited LPS‐induced STAT3 phosphorylation, which was reversed by Compound C treatment. We conclude that AMPK activation is important for NaSal‐mediated inflammation by inducing apoptosis, reducing cell proliferation, inhibiting STAT3 activity, and producing TNF‐α and IL‐1β.
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影响因子：
4.8
作者：
Liu, Chao;Liang, Bin;Zou, Ming-Hui
通讯作者：
Zou, Ming-Hui
二甲双胍通过下调 Stat3 信号促进食管鳞状细胞癌自噬和凋亡
影响因子：
9
作者：
通讯作者：
--
影响因子：
6.1
作者：
Chanput, Wasaporn;Mes, Jurriaan;Wichers, Harry J.
通讯作者：
Wichers, Harry J.
影响因子：
14.9
作者：
KELMAN, Z;ODONNELL, M
通讯作者：
ODONNELL, M
DOI：
10.1126/science.1215327
发表时间：
2012-05-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
通讯作者：
Hardie DG