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载脂蛋白 E 缺乏导致幼鼠肝脏细胞因子表达改变。

Lack of apoE causes alteration of cytokines expression in young mice liver.

机构信息

The Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, 250014, Jinan, People's Republic of China.

出版信息

Mol Biol Rep. 2010 Apr;37(4):2049-54. doi: 10.1007/s11033-009-9660-x. Epub 2009 Jul 31.

DOI:10.1007/s11033-009-9660-x
PMID:19644765
Abstract

To investigate the effect of apolipoprotein E (apoE) on cytokine expression profile of the liver of young mice, quantitative RT-PCR (qRT-PCR) assay and cytokine antibody array for multiplex analysis of 62 cytokines have been used to analyze characteristics of expression of cytokines in the liver of 6-week-old apoE-null (apoE(-/-)) mice. The levels of plasma cytokines were also analyzed. The mRNA level of IL-1 beta, IL-2, IL-6, ICAM-1, VCAM-1, MCP-1, NF-kappaB (p65), IFN-gamma and I kappaB-alpha were increased significantly in apoE(-/-) mice comparative to wild-type (WT) mice. IL-4, IL-10 and GM-CSF, however, were slightly decreased. Compared with WT, levels of 21 cytokines altered twofold or more in apoE(-/-) mice, including 10 cytokines increased and 11 decreased. Expression patterns of IL-1 beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma and VCAM-1 showed identical trend between cytokine antibody array and qRT-PCR analysis. Moreover, levels of IL-1 beta, IFN-gamma and IL-6 in the plasma were elevated, while IL-4 was lightly decreased in apoE(-/-) mice compared to those in WT mice. These results implied that promotion of type I immune response in the liver of young apoE(-/-) mice due to alteration of these cytokines, and the phenotypes may be caused by the regulation of NF-kappaB. The inflammation and lipid metabolism dysfunction in the liver cooperated in dysfunction of the liver in young apoE(-/-) mice.

摘要

为了研究载脂蛋白 E (apoE) 对年轻小鼠肝脏细胞因子表达谱的影响,采用定量 RT-PCR (qRT-PCR) 检测和细胞因子抗体芯片对 62 种细胞因子进行了多重分析,以分析 6 周龄 apoE 基因敲除 (apoE(-/-)) 小鼠肝脏中细胞因子表达特征。还分析了血浆细胞因子水平。apoE(-/-) 小鼠中白细胞介素 1β (IL-1β)、白细胞介素 2 (IL-2)、白细胞介素 6 (IL-6)、细胞间黏附分子 1 (ICAM-1)、血管细胞黏附分子 1 (VCAM-1)、单核细胞趋化蛋白 1 (MCP-1)、核因子-κB (p65)、干扰素-γ (IFN-γ) 和 IκB-α的 mRNA 水平显著高于野生型 (WT) 小鼠。然而,IL-4、IL-10 和 GM-CSF 则略有下降。与 WT 相比,apoE(-/-) 小鼠中有 21 种细胞因子的水平变化了两倍或更多,其中 10 种增加,11 种减少。在细胞因子抗体芯片和 qRT-PCR 分析中,IL-1β、IL-2、IL-4、IL-6、IL-10、GM-CSF、IFN-γ和 VCAM-1 的表达模式呈现出相同的趋势。此外,与 WT 相比,apoE(-/-) 小鼠的血浆中 IL-1β、IFN-γ 和 IL-6 水平升高,而 IL-4 水平略有降低。这些结果表明,由于这些细胞因子的改变,年轻 apoE(-/-) 小鼠肝脏中 I 型免疫反应增强,表型可能是由 NF-κB 调节引起的。年轻 apoE(-/-) 小鼠肝脏中的炎症和脂质代谢功能障碍共同导致了肝脏功能障碍。

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2
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