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高胰岛素状态下巨噬细胞PPARγ抗炎活性的变化(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2006年第1期
页码:
14-17,27
栏目:
基础研究
出版日期:
2006-01-01

文章信息/Info

Title:
Changes in macrophage PPAR gamma antiinflammatory activities under high insulin levels
作者:
张俊峰1葛恒1郭炳诗2王长谦1
1.上海交通大学医学院附属第二医院心内科,上海 200001;2.上海第二医科大学/中国科学院上海生命科学院健康科学中心,上海 200025
Author(s):
ZHANG Jun-feng1GE Heng1GUO Bing-shi2WANG Chang-qian1
1.Department of Cardiology,Renji Hospital,Shanghai Jiaotong University,Shanghai 200001,China; 2. Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai 200025,China
关键词:
胰岛素巨噬细胞过氧化物酶体增殖物激活受体炎症
Keywords:
insulin macrophage peroxisome proliferatoractivated receptors inflammation
分类号:
R329.26
DOI:
-
文献标识码:
A
摘要:
目的 探讨高胰岛素状态下巨噬细胞过氧化物酶体增殖物激活受体γ(PPARγ)抗炎活性的变化。方法 体外培养THP1细胞,诱导分化为巨噬细胞,采用吡格列酮和不同浓度胰岛素分组干预,ELISA法测定细胞培养上清液中IL-6、TNF-α、MMP-9浓度,Gelatin Zymography法测MMP9活性。半定量RTPCR、Western blot检测巨噬细胞PPARγ基因、蛋白表达。结果 PPARγ配体吡格列酮(20 μmol/L)作用24 h可显著降低巨噬细胞IL-6(P<0.01)、TNF-α、MMP-9的分泌(P<0.05),抑制MMP9活性(P<0.05)。高胰岛素使吡格列酮抑制巨噬细胞分泌IL6、TNFα、MMP-9的作用减弱,此作用与胰岛素浓度有关,呈浓度依赖性(0.25~0.5 μmol/L)。而高胰岛素(0.1 μmol/L)状态下巨噬细胞PPARγ基因、蛋白的表达均无显著变化。结论 高胰岛素可减弱PPARγ配体抑制巨噬细胞分泌IL6、TNFα、MMP-9的作用,但并未对巨噬细胞PPARγ基因、蛋白的表达产生影响,提示胰岛素对PPARγ的活性可能存在抑制。
Abstract:
AIM To investigate the changes of the antiinflammatory activities of macrophage PPAR gamma under high insulin levels. METHODS Human monocytic cell lines THP-1 were cultured and then induced into macrophage by PMA treatment. The differentiated monocytes were then cultured in medium of insulin at different concentrations treated with or without piogiltazone. IL-6, TNF-α and MMP-9 levels in cell culture medium were measured by ELISA. MMP-9 activities were determined by gelatin zymography. Macrophage PPARγ mRNA and protein expression were detected by semiquantitative RTPCR and Western blot, respectively. RESULTS Pioglitazone(20 μmol/L) treatment for 24 hours significantly decreased the secretion of IL6 (P<0.01), TNF-α and MMP-9 (P<0.05) from macrophages as well as inhibited MMP-9 activity (P<0.05). High insulin(0.25 μmol/L)partly counteracted the inhibitory action of pioglitazone on macrophage secretion of IL6, TNFα and MMP-9 in a concentrationdependent manner. High insulin(0.1 μmol/L)treatment had no significant effect on macrophage PPARγ mRNA or protein expression. CONCLUSION High insulin can counteract the inhibitory action of PPARγ agonists on macrophage secretion of IL-6, TNF-α and MMP-9, but has no significant effect on macrophage PPARγ mRNA or protein expression, suggesting that insulin may inhibit the activity of PPARγ.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2004-08-20.基金项目:国家自然基金项目资助(No.30070869) 通讯作者:王长谦,主任医师,博士Email:wcqian@hotmail.com 作者简介:张俊峰,主治医师,硕士 Tel:(021)566911016260 Email:zhangjf1222@yahoo.com
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