Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
Food Funct. 2012 Dec;3(12):1286-93. doi: 10.1039/c2fo30023k.
The anti-inflammatory effects of curcuminoids have been extensively investigated. However, few studies investigate the mechanistic involvement of microRNAs (miRNAs) in their activity. The objective of this study was to examine the protective effects of standardized curcuminoid extract (SCE) in vascular inflammation of human umbilical vein endothelial cells (HUVEC) and the potential involvement of miRNA-126 and miRNA-146a. Escherichia coli lipopolysacharides (LPS) were used to induce inflammation. LPS-challenge increased gene-expression of toll-like receptor-4 (TLR-4) and downstream genes IL-1 receptor-associated kinase 1 (IRAK-1) and tumor necrosis factor receptor-associated factor 6 (TRAF-6) up to 2.58-, 2.39-, and 3.73-fold, respectively, relative to DMSO-treated controls that were not challenged with LPS. LPS up-regulated TLR-4, IRAK-1, and TRAF-6 in SCE pretreated cells (5 mg L(-1)), only up to 0.69-, 1.28-, and 1.15-fold, respectively. miRNA-146a can be up-regulated by transcription nuclear factor kappa B (NF-κB) and acts as a negative feedback loop regulator involving IRAK-1 and TRAF-6 downregulation. In this study, the down-regulation of NF-κB was accompanied by reduced miRNA-146a expression. LPS-challenge induced mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) up to 5.65- and 10.65-fold, respectively. SCE prevented this effect and increases of up to only 2.92- and 5.26-fold of DMSO-treated controls not challenged with LPS were observed. miRNA-126 regulates endothelial expression of VCAM-1, but was not inversely correlated to the expression of its target gene VCAM-1 upon SCE treatment; therefore, miRNA-126 does not appear to be involved in the down-regulation of VCAM-1. Overall, curcuminoids are confirmed to have anti-inflammatory properties in HUVEC; however, neither miRNA-146a nor miRNA-126 seem to be involved in the SCE-induced down-regulation of the NF-κB-target genes IRAK-1, TRAF-6, and VCAM-1.
姜黄素类化合物的抗炎作用已得到广泛研究。然而，很少有研究探讨 microRNAs（miRNAs）在其活性中的机制作用。本研究的目的是研究标准化姜黄素提取物（SCE）对人脐静脉内皮细胞（HUVEC）血管炎症的保护作用，以及 miRNA-126 和 miRNA-146a 的潜在作用。大肠杆菌脂多糖（LPS）用于诱导炎症。LPS 刺激使 Toll 样受体-4（TLR-4）及其下游基因白细胞介素-1 受体相关激酶 1（IRAK-1）和肿瘤坏死因子受体相关因子 6（TRAF-6）的基因表达分别增加至 2.58、2.39 和 3.73 倍，与未用 LPS 刺激的 DMSO 处理对照组相比。LPS 在 SCE 预处理细胞（5mgL(-1)）中上调 TLR-4、IRAK-1 和 TRAF-6，仅分别上调至 0.69、1.28 和 1.15 倍。miRNA-146a 可被转录核因子 kappa B（NF-κB）上调，并作为涉及 IRAK-1 和 TRAF-6 下调的负反馈回路调节剂。在本研究中，NF-κB 的下调伴随着 miRNA-146a 表达的减少。LPS 刺激使血管细胞粘附分子-1（VCAM-1）和细胞内细胞粘附分子-1（ICAM-1）的 mRNA 水平分别增加至 5.65 和 10.65 倍。SCE 可防止这种作用，而 LPS 未刺激的 DMSO 处理对照组的增加仅观察到 2.92 和 5.26 倍。miRNA-126 调节内皮细胞 VCAM-1 的表达，但在 SCE 处理后与 VCAM-1 靶基因的表达呈负相关，因此 miRNA-126 似乎不参与 VCAM-1 的下调。总体而言，姜黄素类化合物在 HUVEC 中被证实具有抗炎作用；然而，miRNA-146a 和 miRNA-126 似乎都不参与 SCE 诱导的 NF-κB 靶基因 IRAK-1、TRAF-6 和 VCAM-1 的下调。
