Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages
Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages
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DOI：
10.1007/s10753-012-9495-9
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发表时间：
2012-12-01
期刊：
影响因子：
5.1
通讯作者：
Feng, Haihua
中科院分区：
文献类型：
--
作者：
Guo, Weixiao;Sun, Jingjing;Feng, Haihua
欧前胡素是一种香豆素化合物，具有抗菌和抗病毒活性。在本研究中，我们通过研究欧前胡素对细胞因子产生和表达以及主要信号转导途径的影响，研究了欧前胡素在脂多糖 (LPS) 刺激的 RAW 264.7 巨噬细胞中的抗炎作用。我们发现欧前胡素以浓度依赖性方式下调LPS诱导的RAW 264.7巨噬细胞中TNF-α、IL-1β和IL-6的水平，并且显着抑制TNF-α和IL-6的表达（P < 0.05或P < 0.01）。通过蛋白质印迹分析丝裂原激活蛋白激酶和核因子-kappaB (NF-kappa B) p65 蛋白的磷酸化。在用 1 mg/L LPS 处理的 RAW 264.7 巨噬细胞中，欧前胡素显着抑制 p38 和 Jun N 末端激酶磷酸化蛋白的表达。然而，p-ERK 没有显着变化。此外，欧前胡素还通过阻断 I kappa B α 磷酸化和降解来抑制 NF-kappa B 易位到细胞核中。
Imperatorin is a type of coumarin compound with antibacterial and antiviral activities. In the present study, we examined the anti-inflammatory effects of imperatorin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found that imperatorin downregulated LPS-induced levels of TNF-alpha, IL-1 beta, and IL-6 in RAW 264.7 macrophages in a concentration-dependent manner, and it significantly inhibited expression of TNF-alpha and IL-6 (P < 0.05 or P < 0.01). The phosphorylation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-kappa B) p65 protein were analyzed by western blotting. In RAW 264.7 macrophages treated with 1 mg/L of LPS, imperatorin significantly inhibited p38 and Jun N-terminal kinase phosphorylation protein expression. However, there was no significant change in p-ERK. Furthermore, imperatorin also inhibited NF-kappa B translocation into the nucleus through blockage of I kappa B alpha phosphorylation and degradation.