The Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, #88 East Wenhua Ave., Jinan 250014, China.
Mol Cell Biochem. 2012 Jul;366(1-2):59-67. doi: 10.1007/s11010-012-1283-1. Epub 2012 Mar 10.
Both the aorta and the liver are major organs that play important roles in lipid metabolism, and they are subject to systemic as well as local inflammatory responses in metabolic syndrome. Our previous study indicated that TNFα deficiency influences atherogenesis by reducing inflammation of the aorta. To better understand this phenomenon, the mRNA and protein expression profiles of a panel of cytokines in the aorta and liver of young TNFα-null (TNFα(-/-)) mice were analyzed and compared with age- and gender-matched wild-type (WT) control mice. In the aorta, IL-2 and GM-CSF were up-regulated versus WT mice, while IL-1β, IL-4, IL-6, IL-10, MCP-1, IFN-γ, and the adhesion molecules ICAM-1 and VCAM-1 were down-regulated. In the liver, however, the expressions of NF-κB, IL-1, IL-2, IL-6, IL-10, ICAM-1, and VCAM-1 were significantly up-regulated in TNFα(-/-) mice, while IFN-γ and IL-4 were down-regulated. Out of the 62 cytokines analyzed, 22 in the aorta and 27 in the liver were altered by 2-fivefolds at the protein level in TNFα(-/-) mice. Our data demonstrated that the loss of TNFα function led to various changes in the levels of cytokine expression in these organs at both the transcriptional and translational levels. These results indicated that the changes in cytokine expression patterns in the aorta and the liver may further influence the progression of systemic or local lipid metabolism dysregulation and pathogenesis in animals with TNFα dysfunction representing inflammation-related diseases, such as atherosclerosis and metabolic syndrome.
主动脉和肝脏都是在脂质代谢中发挥重要作用的主要器官，它们在代谢综合征中既受到系统性炎症反应的影响，也受到局部炎症反应的影响。我们之前的研究表明，TNFα 缺乏通过减少主动脉炎症来影响动脉粥样硬化的形成。为了更好地理解这一现象，我们分析并比较了年轻的 TNFα 缺失（TNFα(-/-)）小鼠和年龄及性别匹配的野生型（WT）对照小鼠主动脉和肝脏中一组细胞因子的 mRNA 和蛋白表达谱。在主动脉中，与 WT 小鼠相比，IL-2 和 GM-CSF 的表达上调，而 IL-1β、IL-4、IL-6、IL-10、MCP-1、IFN-γ 以及黏附分子 ICAM-1 和 VCAM-1 的表达下调。然而，在肝脏中，TNFα(-/-)小鼠中 NF-κB、IL-1、IL-2、IL-6、IL-10、ICAM-1 和 VCAM-1 的表达显著上调，而 IFN-γ 和 IL-4 的表达下调。在分析的 62 种细胞因子中，22 种在主动脉中，27 种在肝脏中，其蛋白水平在 TNFα(-/-)小鼠中改变了 2-5 倍。我们的数据表明，TNFα 功能的丧失导致这些器官中细胞因子表达水平在转录和翻译水平上发生了各种变化。这些结果表明，主动脉和肝脏中细胞因子表达模式的变化可能进一步影响 TNFα 功能障碍动物全身或局部脂质代谢失调和发病机制的进展，代表与炎症相关的疾病，如动脉粥样硬化和代谢综合征。
