Pravastatin down-regulates inflammatory mediators in human monocytes in vitro
Pravastatin down-regulates inflammatory mediators in human monocytes in vitro
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DOI：
10.1016/s0014-2999(00)00870-0
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发表时间：
2000-12-20
影响因子：
5
通讯作者：
Lindgren, S
中科院分区：
文献类型：
--
作者：
Grip, O;Janciauskiene, S;Lindgren, S
实验证明，普伐他汀可以抑制胆固醇合成的限速酶，从而影响细胞的代谢和增殖。因此，我们在体外研究了普伐他汀对非刺激和刺激原代人单核细胞炎症介质生成的影响。在我们的实验模型中，普伐他汀诱导单核细胞胆固醇合成的剂量依赖性抑制（高达67%），低密度脂蛋白受体mRNA的上调（约35%）和细胞内胆固醇积累的减少。同时，未受刺激的单核细胞暴露于不同剂量的普伐他汀导致单核细胞趋化蛋白-1蛋白表达的抑制（高达15倍），肿瘤坏死因子α (tnf - α)水平的降低（高达2.4倍）和受刺激细胞中金属蛋白酶-9活性的完全丧失。5、100和500 muM浓度的普伐他汀对tnf - α诱导的细胞耗氧量的抑制作用为2.4- 5.5倍。这些数据扩展了他汀类药物潜在抗炎作用的发现，也表明普伐他汀在更广泛的炎症情况下使用的可能性。(C) 2000 Elsevier Science B.V.版权所有
There is experimental evidence that pravastatin, which is designed to inhibit the rate-limiting enzyme of cholesterol synthesis, can affect cell metabolism and proliferation. We therefore studied the effects of pravastatin on the generation of inflammatory mediators in non-stimulated and stimulated primary human monocytes in vitro. In our experimental model, pravastatin induced a dose-dependent inhibition of monocyte cholesterol synthesis (up to 67%), up-regulation of low density lipoprotein receptor mRNA (by about 35%) and reduction in intracellular cholesterol accumulation. In parallel, exposure of non-stimulated monocytes to various doses of pravastatin resulted in inhibition of monocyte chemoattractant protein-1 protein expression (up to 15-fold), reduction of tumour necrosis factor alpha (TNF-alpha) levels (up to 2.4-fold) and a total loss of metalloproteinase-9 activity in stimulated cells. Pravastatin at concentrations of 5, 100 and 500 muM caused an inhibition of TNF-alpha -induced cellular oxygen consumption from 2.4- to 5.5-fold. These data extend the findings of potential anti-inflammatory actions of statins and also suggest the possibility for pravastatin use in a broader spectrum of inflammatory situations. (C) 2000 Elsevier Science B.V. All rights reserved.