Role of Plant Sterol and Sterolin in Macrophages and T Lynphocytes

植物甾醇和甾醇在巨噬细胞和 T 淋巴细胞中的作用

基本信息

批准号：
18590977
负责人：
TSUKAMOTO Kazuhisa
金额：
$ 2.53万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590977/
关键词：
macrophage plant sterol inflammation cytokine sterolin atherosclerosis

项目摘要

It has been known that the gene mutations in ABCG5 or ABCG8 result in phytosterolemia which is characterized with the premature atherosclerosis. However, the precise mechanism underlying in the atherogenesis in phytosterolemia has not been elucidated. In this study, we evaluated gene expressions of ABCG5 and ABCG8 in macrophages, and sterol-induced cytokine production in macrophages. Human macrophages, mouse peritoneal macrophages, J774. Al cells and RAW264.7 cells were utilized in this study. Neither ABCG5 nor ABCG8 were expressed in macrophages; even the cholesterol loading or stimulation with LXR agonist to the cells did not result in the expressions. The cells were loaded with cholesterol, sitosterol or campesterol in low (16 uM) and high (160 uM) concentrations, and cytokines production from the cells were examined. When the sterols were loaded to RAW264.7 cells in low concentration, sitosterol induced slight increase in cytokines in case they were stimulated with LPS. In high sterol loading with LPS stimulation, cholesterol induced prominent increase in cytokine production in both J774. Al cells and RAW264.7 cells, while sitosterol and campesterol reduced the production of cytokines. Due to the accidents of the animal facility of the Tokyo University, we could not perform sufficient animal experiments; however, the preliminary study revealed that the plasma total cholesterol levels and cytokine levels in the double knock out mice in apoE and sterolins might be lower than those of apoE deficient mice. These results indicate that the macrophages would not the main player in the atherogenesis of phytosterolemia. Through this study, we found that the splicing of ABCG5 cDNA in the liver is different from that in the intestine, which suggests that the sterolin 1 in the liver would behave differently from that in the intestine.

众所周知，ABCG5或ABCG8中的基因突变会导致植物度血症，其特征是动脉粥样硬化。然而，未来植物学血症的动脉粥样硬化中的确切机制尚未阐明。在这项研究中，我们评估了巨噬细胞中ABCG5和ABCG8的基因表达，以及固醇诱导的巨噬细胞的细胞因子产生。人类巨噬细胞，小鼠腹膜巨噬细胞，J774。在这项研究中使用了Al细胞和RAW264.7细胞。 ABCG5和ABCG8均未在巨噬细胞中表达。即使是用LXR激动剂刺激或刺激细胞的胆固醇载荷或刺激也不会导致表达。细胞在低（16 um）和高（160 um）浓度的胆固醇，羟基苯酚或campsterol加载，并检查细胞因子产生的细胞因子。当将固醇以低浓度的固醇加载到RAW264.7细胞中时，如果通过LPS刺激了细胞因子的细胞因子略微增加。在用LPS刺激的高固醇载荷中，胆固醇在J774中诱导细胞因子产生显着增加。 Al细胞和RAW264.7细胞，而羟基苯酚和campesterol降低了细胞因子的产生。由于东京大学动物设施的事故，我们无法进行足够的动物实验。但是，初步研究表明，在ApoE和固醇中，血浆总胆固醇水平和细胞因子水平可能低于APOE缺乏小鼠。这些结果表明，巨噬细胞不会成为植物性血症动脉粥样硬化的主要参与者。通过这项研究，我们发现肝脏中ABCG5 cDNA的剪接与肠中的剪接不同，这表明肝脏中的固醇1与肠道的行为不同。