Eicosapentaenoic acid inhibits interleukin-6 production in interleukin-1β-stimulated C6 glioma cells through peroxisome proliferator-activated receptor-gamma
Eicosapentaenoic acid inhibits interleukin-6 production in interleukin-1β-stimulated C6 glioma cells through peroxisome proliferator-activated receptor-gamma
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DOI：
10.1016/j.plefa.2008.07.002
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发表时间：
2008-07-01
影响因子：
3
通讯作者：
Mizuguchi, Kiyoshi
中科院分区：
文献类型：
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作者：
Kawashima, Akiko;Harada, Tsuyoshi;Mizuguchi, Kiyoshi
流行病学研究表明，摄入omega-3多不饱和脂肪酸可以改善阿尔茨海默病等表现为炎症病理的神经系统疾病。因此，我们研究了二十碳五烯酸(EPA)对白细胞介素1(IL)-1β刺激的C6胶质瘤细胞的抗炎作用。在目前的研究中，EPA以剂量依赖的方式抑制IL-1β刺激的C6胶质瘤细胞中促炎症细胞因子IL-6的产生，这是某些神经退行性疾病的特征。EPA在mRNA水平下调IL-6的表达，提示EPA的作用发生在转录水平。此外，PPARγ拮抗剂可阻断EPA对IL-1β诱导的IL-6产生的抑制作用，而PPARα拮抗剂不能阻断EPA的抑制作用。因此，EPA可能通过与PPAR-γ相互作用来调节星形胶质细胞中促炎细胞因子的产生。在本研究中测试的PPARγ配体中，PPARγ的合成激动剂齐格列酮有效地抑制IL-6的产生，而罗格列酮和15-脱氧-Delta(12，14)-前列腺素J(2)都不能抑制IL-6的产生。这些发现表明，PPAR-γ配体的配位在抑制C6胶质瘤细胞产生IL-6方面起着重要作用。(C)2008爱思唯尔有限公司。保留所有权利。
Epidemiological studies suggest that intake of omega-3 polyunsaturated fatty acids improves neurological disorders such as Alzheimer's disease which exhibit inflammatory pathology. We therefore investigated the anti-inflammatory effects of eicosapentaenoic acid (EPA) on interleukin (IL)-1 beta-stimulated C6 glioma cells. In the present study, EPA inhibited pro-inflammatory cytokine IL-6 production, a characteristic of certain neurodegenerative disorders, in IL-1 beta-stimulated C6 glioma cells in dose-dependent fashion. EPA down-regulated the expression of IL-6 at mRNA level, indicating that the effect of EPA occurs at the transcriptional level. In addition, peroxisome proliferator-activated receptor (PPAR) gamma antagonists abolished the inhibitory effect of EPA on IL-1 beta-induced IL-6 production, whereas PPAR alpha antagonist did not block the inhibitory effect of EPA. EPA might thus contribute to the regulation of pro-inflammatory cytokine production in astrocytes through interaction with PPAR gamma. Among the PPAR gamma ligands tested in this study, ciglitazone, a synthetic agonist of PPAR gamma, effectively inhibited IL-6 production, but while neither rosiglitazone nor 15-deoxy-Delta(12,14)-prostaglandin J(2) did. These findings indicate that the coordination of PPAR gamma ligands is important in inhibiting the production of IL-6 in C6 glioma cells. (C) 2008 Elsevier Ltd. All rights reserved.