Increased toll-like receptor activity in patients with metabolic syndrome.
Increased toll-like receptor activity in patients with metabolic syndrome.
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DOI：
10.2337/dc11-2375
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发表时间：
2012-04
期刊：
影响因子：
16.2
通讯作者：
Devaraj S
中科院分区：
文献类型：
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作者：
Jialal I;Huet BA;Kaur H;Chien A;Devaraj S
代谢综合征(METS)非常普遍，并增加了患糖尿病和心血管疾病(CVD)的风险。虽然甲硫氨酸是一种促炎状态，但关于甲硫氨酸的细胞炎症的数据很少。Toll样受体是天然免疫反应的经典模式识别受体。由于单核细胞TLR2和TLR4与动脉粥样硬化和胰岛素抵抗有关，本研究的目的是检测无糖尿病和心血管疾病的METS患者和对照组的单核细胞TLR2和TLR4。空腹取血检测TLR的表达和活性。调整腰围后，METS患者循环中高敏C反应蛋白、IL-1β、IL-6、IL-8和可溶性肿瘤坏死因子受体1(sTNFR-1)水平显著高于对照组。调整腰围后，TLR2和TLR4的表面表达和单核细胞上的mRNA均显著增加。除了核因子-κB核结合增加外，单核细胞经脂多糖刺激后，蛋氨酸组IL-1β、IL-6和IL-8的释放显著高于对照组。血浆游离脂肪酸和内毒素在蛋氨酸组均升高，但仅与TLR4显著相关。总之，我们进行了新的观察，即TLR2和TLR4在METS患者单核细胞中的表达和活性均增加，并可能导致糖尿病和心血管疾病风险的增加。
The metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response. The aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity. Circulating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only. In conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.