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Involvement of WSX-1 in atherosclerosis

WSX-1 参与动脉粥样硬化

基本信息

批准号：
17590748
负责人：
HIRASE Tetsuaki
金额：
$ 1.41万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590748/
关键词：
cardiovascular disease atherosclerosis inflammation cvtokine

项目摘要

Atherosclerosis is a chronic inflammatory disease. It has been shown that cytokines play important roles in vascular inflammation in atherosclerosis. IL-27 that is a member of IL-12 family regulates Th1 cell differentiation and production of inflammatory cytokines from T cells. In this study, we aimed to examine the involvement of EBI3, a component of IL-27, and WSX-1, a component of IL-27 receptor, in atherosclerosis.We crossed EBI3 knockout mice and WSX-1 knockout mice with atherosclerosis-prone LDL receptor knockout mice to generate double knockout mice. LDL receptor knockout mice and double knockout mice were fed with high cholesterol diet for 16 weeks from the age of 8 weeks old. Body weight, blood pressure and serum cholesterol levels showed no significant differences among LDL receptor knockout mice and double knockout mice. Atherosclerotic lesions in aorta stained with oil red O were larger in double knockout mice than in LDL receptor knockout mice. Areas stained with MOMA-2, a macrophage marker, in atherosclerotic lesions were larger in double knockout mice than in LDL receptor knockout mice.These data suggest that deficiency of EBI3 and WSX-1 promotes atherosclerosis through macrophage activation. Further studies are necessary to elucidate the molecular mechanisms responsible for macrophage activation in deficiency of EBI3 and WSX-1.

动脉粥样硬化是一种慢性炎性疾病。研究表明，细胞因子在动脉粥样硬化的血管炎症中起重要作用。IL-27是IL-12家族的成员，它调节Th1细胞的分化和T细胞炎症因子的产生。在这项研究中，我们旨在研究IL-27的组成部分EBI3和IL-27受体的组成部分WSX-1在动脉粥样硬化中的作用。我们将EBI3敲除小鼠和WSX-1敲除小鼠与动脉粥样硬化易发LDL受体敲除小鼠杂交，生成双敲除小鼠。LDL受体敲除小鼠和双敲除小鼠从8周龄开始饲喂高胆固醇饲料16周。LDL受体敲除小鼠和双敲除小鼠的体重、血压和血清胆固醇水平无显著差异。双敲除小鼠主动脉油红O染色的动脉粥样硬化病变比LDL受体敲除小鼠大。双敲除小鼠的动脉粥样硬化病变中，巨噬细胞标记物MOMA-2染色的区域比LDL受体敲除小鼠大。这些数据表明，缺乏EBI3和WSX-1通过巨噬细胞激活促进动脉粥样硬化。在EBI3和WSX-1缺乏的情况下，巨噬细胞活化的分子机制有待进一步研究。