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首页> 外文期刊>Cytokine >TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes
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TNF-α modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes

机译：TNF-α调节他汀类药物对3T3-L1分化的脂肪细胞分泌MCP-1，PAI-1和脂联素的作用

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Purpose: Systemic inflammatory conditions, as seen in obesity and in the metabolic syndrome, are associated with high plasmatic levels of proatherogenic and prothromboticadipokines and low levels of adiponectin. Inhibitors of HMG-CoA reductase have beneficial effects in reducing cardiovascular events attributed predominantly to its lipid-lowering effects and recent studies suggest that these effects might be due to its anti-inflammatory properties. Based on the pleiotropic properties of simvastatin we studied the effects of this drug on the secretion and expression of adiponectin, PAI-1 and MCP-1 in mature adipocytes under baseline conditions and after an inflammatory stimulation. Materials and methods: The differentiated adipocytes were incubated with 10μM simvastatin or vehicle and TNF-α 10. ng/mL or vehicle were added to treatment media. After 24. h of incubation, the media was harvested and the proteins of interest were analyzed by Multiplex method. Gene expression was analyzed by real time-PCR. Results: The addition of TNF-α increased the expression and secretion of MCP-1 and PAI-1. However, stimulation did not interfere with the secretion of adiponectin, despite having significantly reduced its expression. Our data also demonstrated that simvastatin reduced the expression and secretion of MCP-1, under baseline (770.4 ± 199.9 vs 312.7 ± 113.7 and 1.00 ± 0.14 vs 0.63 ± 0.13, p<0.05, respectively) and inflammatory conditions (14945 ± 228.7 vs 7837.6 ± 847.4 and 24.16 ± 5.49 vs 14.97 ± 2.67, p<0.05, p<0.05, respectively). Simvastatin also attenuated the increase in expression and secretion of PAI-1 induced by TNF-α (16898.6 ± 1663.3 vs 12922.1 ± 843.9 and 5.19 ± 3.12 vs 0.59 ± 0.16, respectively p<0.05), but under baseline conditions had no effect on the expression or secretion of PAI-1. The statin increased the expression of adiponectin under baseline conditions and inflammatory stimulation (1.03 ± 0.08 vs 4.0 ± 0.96 and 0.77 ± 0.19 vs 2.16 ± 0.23, respectively, p<0.05) and also increased the secretion of this adipokine but only with the inflammatory stimulus (5347.7 ± 1789.3 vs 7327.3 ± 753.6, p<0.05). Conclusions: Our findings suggested that simvastatin counteracted the stimulatory effect of TNF-α on secretion and expression of MCP-1, PAI-1 and adiponectin, implying a potential anti-atherogenic effect during the inflammatory process; these pleitropic effects were more pronounced with HMG-CoA reductase inhibitor.
机译：目的：在肥胖症和代谢综合征中观察到的全身性炎症与血浆中高水平的促动脉粥样硬化和血栓形成前的促血小板生成素以及低水平的脂联素有关。 HMG-CoA还原酶抑制剂在减少心血管事件方面具有有益作用，这主要归因于其降脂作用，最近的研究表明，这些作用可能归因于其抗炎特性。基于辛伐他汀的多效性，我们研究了该药物对基线条件下和炎症刺激后成熟脂肪细胞中脂联素，PAI-1和MCP-1分泌和表达的影响。材料和方法：将分化的脂肪细胞与10μM辛伐他汀或媒介物温育，然后将TNF-α10 ng / mL或媒介物添加至治疗培养基中。温育24小时后，收获培养基，并通过Multiplex方法分析目的蛋白质。通过实时PCR分析基因表达。结果：添加TNF-α可增加MCP-1和PAI-1的表达和分泌。然而，刺激虽然显着降低了脂联素的表达，但并未干扰脂联素的分泌。我们的数据还表明，辛伐他汀在基线状态（分别为770.4±199.9 vs 312.7±113.7和1.00±0.14 vs 0.63±0.13，p <0.05）和炎性条件（14945±228.7 vs 7837.6）下会降低MCP-1的表达和分泌。 ±847.4和24.16±5.49与14.97±2.67，分别为p <0.05，p <0.05）。辛伐他汀还减弱了TNF-α诱导的PAI-1表达和分泌的增加（分别为16898.6±1663.3 vs 12922.1±843.9和5.19±3.12 vs 0.59±0.16，p <0.05），但在基线条件下对PAI-1没有影响。 PAI-1的表达或分泌。他汀类药物在基线条件和炎症刺激下分别增加脂联素的表达（分别为1.03±0.08 vs 4.0±0.96和0.77±0.19 vs 2.16±0.23，p <0.05），并且还增加了这种脂肪因子的分泌，但仅在炎症刺激下（5347.7±1789.3与7327.3±753.6，p <0.05）。结论：我们的发现提示辛伐他汀可抵消TNF-α对MCP-1，PAI-1和脂联素分泌和表达的刺激作用，暗示在炎症过程中可能具有抗动脉粥样硬化作用。使用HMG-CoA还原酶抑制剂，这些多效作用更为明显。

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