Moderate alcohol intake in humans attenuates monocyte inflammatory responses: Inhibition of nuclear regulatory factor kappa B and induction of interleukin 10
Moderate alcohol intake in humans attenuates monocyte inflammatory responses: Inhibition of nuclear regulatory factor kappa B and induction of interleukin 10
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DOI：
10.1111/j.1530-0277.2006.00012.x
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发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Szabo, G
中科院分区：
文献类型：
--
作者：
Mandrekar, P;Catalano, D;Szabo, G
背景资料：与长期过量饮酒对肝脏和心血管系统的有害影响相反，适度饮酒，如每天1至2杯，对心血管死亡率有好处。对于饮酒时间的长短或饮酒量的多少，人们知之甚少，饮酒可能会导致炎症细胞（如单核细胞）的改变，而单核细胞对动脉粥样硬化性血管疾病至关重要。在这里，我们确定在体内急性酒精消费对炎症细胞因子的产生和核调节因子KB（NF-κ B）结合在人monocytes.Methods：人血单核细胞分离的塑料粘附之前和之后急性酒精消费（2毫升伏特加/公斤体重）。然后通过ELISA测定单核细胞中脂多糖（LPS）和超抗原诱导的肿瘤坏死因子α（TNF α）、白细胞介素（IL）-1 β和IL-10的产生。核调节因子-KB活性的单核细胞之前和之后的酒精消费估计通过电迁移率变动分析和启动子驱动的报告活性。IKB α蛋白质印迹法测定在胞质extracts.Results：18小时后，适度饮酒，我们发现单核细胞产生的炎症介质，TNF-α和IL-1 β，在响应LPS或葡萄球菌肠毒素B刺激显着减少。急性酒精消耗抑制LPS诱导的单核细胞中p65/p50 NF-κ B的DNA结合，调节TNF-α和IL-1 β基因的表达。与此一致，急性酒精治疗（25 mM）显着减少LPS诱导的激活NF-κ B驱动的报告基因，表明抑制这种促炎信号通路。此外，LPS诱导的1 KB α降解不受急性饮酒的影响，表明IL：1 β非依赖性机制，如早期体外急性酒精研究中所观察到的。相比之下，单核细胞生产的抗炎细胞因子，IL-10，增加了急性酒精intake.Conclusions：我们的研究结果表明，急性酒精消费具有双重抗炎作用，涉及增强IL-10和衰减单核细胞炎症反应，涉及抑制NF-κ B。这些机制可能有助于适度饮酒对动脉粥样硬化的有益作用。
Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor KB (NF-KB) binding in human monocytes.Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1 beta, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor-KB activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. IKB alpha was determined by Western blotting in the cytoplasmic extracts.Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF-alpha and IL-1 beta, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF-KB in monocytes that regulates the expression of both the TNF-alpha and the IL-I beta genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF-KB-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced 1KB alpha degradation was not affected by acute alcohol consumption indicating an IL:1 beta-independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake.Conclusions: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF-KB. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis.