Thiazolidinediones inhibit TNFα induction of PAI-1 independent of PPARγ activation
Thiazolidinediones inhibit TNFα induction of PAI-1 independent of PPARγ activation
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DOI：
10.1016/j.bbrc.2005.06.055
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发表时间：
2005-08-19
影响因子：
3.1
通讯作者：
Dear, AE
中科院分区：
文献类型：
--
作者：
Liu, HB;Hu, YS;Dear, AE
在肿瘤坏死因子 α (TNF α) 刺激的内皮细胞中观察到 I 型纤溶酶原激活剂抑制剂 (PAI-1) 水平升高。噻唑烷二酮类 (TZD) 可能会抑制内皮细胞 PAI-1 升高，部分原因是 TZD 具有假定的动脉粥样硬化保护作用。在内皮细胞系中，罗格列酮 (RG) 和吡格列酮 (PG) 抑制 TNF α 对 PAI-1 的诱导。特定的过氧化物酶体增殖物激活受体 γ (PPAR γ) 抑制剂 SR-202 未能调节这种作用。在与显性失活 PPAR-γ 构建体共转染的细胞中，RG 还抑制 TNF α 对含有近端 PAI-1 启动子和 PAI-1 mRNA 的报告基因构建体的影响。 RG 和 PG 减弱 TNF α 介导的反式作用因子 Nur77/Nurr1 的诱导以及核蛋白 (NP) 与顺式作用元件 (NBRE) 的结合。 SR-202 未能调节这些效应。观察结果表明，TZD 抑制 TNF α 介导的 PAI-1 诱导，与诱导性 PPAR γ 激活无关，这可能涉及 Nur77/Nurr1 表达和 NP 与 PAI-1 NBRE 结合的调节。 (c) 2005 Elsevier Inc. 保留所有权利。
Increased plasminogen activator inhibitor type I (PAI-1) levels are observed in endothelial cells stimulated by tumour necrosis factor alpha (TNF alpha). Thiazolidinediones (TZDs) may inhibit elevated endothelial cell PAI-1 accounting, in part, for the putative atheroprotective effects of TZDs. In an endothelial cell line, Rosiglitazone (RG) and Pioglitazone (PG) inhibited induction of PAI-1 by TNF alpha. The specific peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibitor, SR-202, failed to modulate this effect. RG also inhibited the effect of TNF alpha on a reporter gene construct harbouring the proximal PAI-1 promoter and PAI-1 mRNA in cells cotransfected with a dominant-negative PPAR-gamma construct. RG and PG attenuated TNF alpha-mediated induction of trans-acting factor(s) Nur77/Nurr1 and binding of nuclear proteins (NP) to the cis-acting element (NBRE). SR-202 failed to modulate these effects. The observations suggest TZDs inhibit TNF alpha-mediated PAI-1 induction independent of inducible PPAR gamma activation and this may involve in the modulation of Nur77/Nurr1 expression and NP binding to the PAI-1 NBRE. (c) 2005 Elsevier Inc. All rights reserved.