过氧化体增殖物激活型受体δ激动剂抑制RAW264.7细胞炎症因子的表达
DOI:
作者:
作者单位:

作者简介:

通讯作者:

基金项目:


Inhibiting Effects of Peroxisome Proliferator Activated Receptor-δ Activation on Inflammatory Factors in RAW264.7 Cell
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的探讨过氧化体增殖物激活型受体δ激动剂GW0742对氧化型低密度脂蛋白诱导的RAW264.7细胞单核细胞趋化蛋白1、血管细胞黏附分子1、基质金属蛋白酶9基因和蛋白表达的影响。方法构建小鼠过氧化体增殖物激活型受体δ基因干扰慢病毒载体及空病毒载体,将培养的RAW264.7细胞分为对照组、GW0742组、GW0742+过氧化体增殖物激活型受体δ干扰组以及假干扰组,各组均给予氧化型低密度脂蛋白 (50 mg/L)孵育24 h。分别采用逆转录聚合酶链反应和蛋白免疫印迹法检测细胞中单核细胞趋化蛋白1、血管细胞黏附分子1及基质金属蛋白酶9的mRNA及蛋白表达。采用单核细胞趋化实验观察人外周血单核细胞在不同条件培养基中的趋化活性。结果GW0742组细胞中单核细胞趋化蛋白1、血管细胞黏附分子1及基质金属蛋白酶9的mRNA及蛋白表达显著低于对照组(P<0.01或P<0.05),而过氧化体增殖物激活型受体δ干扰显著削弱GW0742对单核细胞趋化蛋白1、血管细胞黏附分子1及基质金属蛋白酶9的抑制作用(P<0.01或P<0.05)。GW0742组单核细胞迁移距离小于对照组(P<0.05),而过氧化体增殖物激活型受体δ干扰能阻断GW0742对单核细胞趋化的抑制作用。结论过氧化体增殖物激活型受体δ激动剂GW0742能显著抑制氧化型低密度脂蛋白诱导的RAW264.7细胞单核细胞趋化蛋白1、血管细胞黏附分子1及基质金属蛋白酶9表达,激活过氧化体增殖物激活型受体δ可能有助于防治动脉粥样硬化。

    Abstract:

    AimTo investigate the effects of peroxisome proliferator activated receptor-δ (PPAR-δ) activation by GW0742 on oxidized low density lipoprotein (ox-LDL)induced upregulation of monocyte chemotactic protein-1 (MCP-1),vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in RAW264.7 cells.MethodsCultured RAW264.7 cells were divided into 4 groups: vehicle-treated group,GW0742-treated group, PPAR-δ silencing+GW0742-treated group and empty vector-transformed group.After stimulated with ox-LDL (50 mg/L) for 24 hours,the mRNA and protein levels of MCP-1, VCAM-1 and MMP-9 were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively.The monocyte migration activity was tested by micropore filter method using a modified Boyden chamber.ResultsBoth the mRNA and protein levels of MCP-1,VCAM-1 and MMP-9 were significantly decreased in GW0742-treated cells compared with vehicle-treated group (P<0.01 or P<0.05 ).However, PPAR-δ gene silencing by RNA interference markedly attenuated these beneficial effects of GW0742 (P<0.01 or P<0.05).Similarly,the monocyte chemotactic activity was noticeably inhibited in GW0742-treated cells (P<0.05),while this inhibitory effect of GW0742 was completely blocked by PPAR-δ gene silencing.ConclusionsThe present study shows that PPAR-δ activation by GW0742 successfully inhibits the oxidized LDL-induced upregulation of MCP-1,VCAM-1 and MMP-9 in RAW264.7 cells and monocyte migration.The results indicates that activating PPAR-δ might become an effective strategy for the prevention of atherosclerosis.

    参考文献
    相似文献
    引证文献
引用本文

杨大春,杨永健,张鑫,李德,唐兵,陈劲松,朱峻,速晓华,李刚.过氧化体增殖物激活型受体δ激动剂抑制RAW264.7细胞炎症因子的表达[J].中国动脉硬化杂志,2010,18(1):37~42.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2009-08-11
  • 最后修改日期:2009-11-24
  • 录用日期:
  • 在线发布日期: