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首页> 外文期刊>Cytokine >Decreased C-reactive protein-induced resistin production in human monocytes by simvastatin.
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Decreased C-reactive protein-induced resistin production in human monocytes by simvastatin.

机译：辛伐他汀可降低人单核细胞中C反应蛋白诱导的抵抗素生成。

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Background: Resistin is a novel cysteine-rich protein that plays a role in the development of insulin resistance and atherosclerosis in rodents, while its role in humans is unclear. C-reactive protein (CRP) is an important risk predictor for coronary heart disease, and it can also modify the expression of genes involved in atherogenesis. Statins have been demonstrated to possess lipid lowering effects as well as pleiotropic properties. We hypothesize that CRP may result in overexpression of resistin, and statin may decrease CRP-induced resistin expression in cultured human peripheral blood monocytes (PBMC). Purpose: The aim of the present study, therefore, was to assess the effects of both CRP on resistin expression and simvastatin on CRP-induced of resistin expression in cultured human PBMC. Methods: Human PBMC were isolated from the whole blood of healthy volunteers by density gradient centrifugation. First, cells were incubated with varying concentrations of CRP (0, 5, 10, 25 and 50mug/ml) for 24h for assessing the dose-dependent effects on resistin expression. Second, 25mug/ml of CRP was used to time-dependent evaluation on resistin expression (0, 3, 6, 12 and 24h). Moreover, cells were pretreated with simvastatin at concentrations from 0.1 to 1muM for 2h, and then co-incubated with 25mug/ml CRP for 24h for evaluating effect of statin on resistin production subjected to CRP. Finally, in additional experiments, monocytes were incubated with 1muM simvastatin in the absence or presence of 100muM mevalonate or 10muM geranylgeranyl-pyrophosphate (GGPP) or 10muM farnesylpyrophosphate (FPP) for 2h, then co-incubated with CRP for 24h for examining whether effects of statin on CRP-induced resistin expression was independent of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Results: The results showed that CRP induced both mRNA expression and protein secretion of resistin in a dose- and time-dependent manner. Co-incubation with simvastatin significantly inhibited CRP-induced up-regulationof mRNA and protein expression of resistin. Treatment with mevalonate, GGPP, but not FPP, reversed the inhibition of resistin expression caused by simvastatin, suggesting that simvastatin regulated resistin expression in culture human PBMC through the mevalonate-GGPP signal pathway. Conclusions: In the present study, the data showed that CRP could significantly increase resistin expression in cultured human PBMC, and this effect was inhibited by simvastatin, suggesting that CRP and resistin might be involved in the pathogenesis of atherosclerosis, and statin therapy might be beneficial for atherosclerotic disease by modifying CRP-induced resistin overexpression in PBMC.
机译：背景：抵抗素是一种新型的富含半胱氨酸的蛋白质，在啮齿类动物的胰岛素抵抗和动脉粥样硬化的发展中起作用，而在人类中的作用尚不清楚。 C反应蛋白（CRP）是冠心病的重要风险预测指标，它还可以修饰动脉粥样硬化相关基因的表达。他汀类药物已证明具有降脂作用和多效性。我们假设CRP可能导致抵抗素的过度表达，而他汀可能降低培养的人外周血单核细胞（PBMC）中CRP诱导的抵抗素表达。目的：因此，本研究的目的是评估CRP对抵抗素表达的影响，以及辛伐他汀对CRP诱导培养的人PBMC中抵抗素表达的影响。方法：通过密度梯度离心从健康志愿者的全血中分离出人PBMC。首先，将细胞与不同浓度的CRP（0、5、10、25和50μg/ ml）孵育24小时，以评估其对抵抗素表达的剂量依赖性作用。其次，使用25 ug / ml的CRP进行抵抗素表达的时间依赖性评估（0、3、6、12和24h）。此外，将细胞用辛伐他汀以0.1至1μM的浓度预处理2h，然后与25mug / ml CRP共同孵育24h，以评估他汀对接受CRP的抵抗素产生的影响。最后，在其他实验中，将单核细胞与1μM辛伐他汀在不存在或存在100μM甲羟戊酸酯或10μM香叶基香叶基焦磷酸酯（FGPP）或10μM法呢基焦磷酸酯（FPP）的情况下孵育2小时，然后与CRP共同孵育24小时，以检查他汀对CRP诱导的抵抗素表达独立于3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂。结果：结果表明，CRP以剂量和时间依赖性方式诱导抵抗素的mRNA表达和蛋白分泌。与辛伐他汀共同孵育可显着抑制CRP诱导的抵抗素mRNA和蛋白表达上调。用甲羟戊酸，GGPP而不是FPP进行的治疗逆转了辛伐他汀对抵抗素表达的抑制作用，表明辛伐他汀通过甲羟戊酸-GGPP信号途径调节了培养的人PBMC中抵抗素的表达。结论：在本研究中，数据显示CRP可以显着增加培养的人PBMC中抵抗素的表达，而辛伐他汀可抑制这种作用，这表明CRP和抵抗素可能参与了动脉粥样硬化的发病机制，他汀类药物疗法可能是有益的通过修饰CRP诱导的PBMC中抵抗素过表达来治疗动脉粥样硬化疾病。

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