The Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, 250014, Jinan, People's Republic of China.
Mol Biol Rep. 2010 Apr;37(4):2049-54. doi: 10.1007/s11033-009-9660-x. Epub 2009 Jul 31.
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.
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。