Red wine polyphenolics reduce the expression of inflammation markers in human colon-derived CCD-18Co myofibroblast cells: Potential role of microRNA-126

Red wine polyphenolics reduce the expression of inflammation markers in human colon-derived CCD-18Co myofibroblast cells: Potential role of microRNA-126
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DOI:
10.1039/c2fo10271d
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发表时间:
2012-07-01
期刊:
影响因子:
6.1
通讯作者:
Mertens-Talcott, Susanne
Mertens-Talcott, Susanne
中科院分区:
农林科学1区
文献类型:
--
作者:
Angel-Morales, Gabriela;Noratto, Giuliana;Mertens-Talcott, Susanne

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慢性肠道炎症是结肠癌的既定危险因素。来自水果和蔬菜的多酚化合物已被证明在几种细胞系和组织中具有抗炎特性。然而,它们的抗炎机制,涉及炎症调节中的microRNA,尚未得到广泛研究。本研究的目的是评估从红葡萄(葡萄属夏葡萄杂种)制成的红葡萄酒中提取的多酚在人结肠来源的CCD-18 Co肌成纤维细胞中的化学预防潜力,并评估microRNA-126(miR-126)在潜在机制中的潜在参与。结果显示多酚红酒提取物(WE)以剂量依赖性方式分别使脂多糖(LPS)诱导的炎症介质NF-κ B、ICAM-1、VCAM-1和PECAM-1的mRNA表达降低1.95倍、1.98倍、1.52倍和1.84倍(0-100 μ g没食子酸当量(GAE)mL(-1))分别下降到DMSO处理的未用LPS攻击的对照细胞的0.80、0.79、0.66和0.68倍。相应地,在VCAM-1 mRNA的3 '-UTR内具有靶区域的miR-126在100 μ g GAE mL(-1)的WE下增加2.79倍。miR-126的潜在作用通过用特异性miR-126-miR-126-as-miR-126转染细胞来证实。转染as-miR-126后,对照细胞中的miR-126下调至0.71倍,NF-kB、ICAM-1、VCAM-1和PECAM-1的mRNA水平分别上调至对照的1.80、1.49、2.30和1.95倍。100 μ g GAE mL(-1)的WE部分逆转了as-miR-126对NF-κ B、ICAM-1、VCAM-1和PECAM-1 RNA水平的影响,分别为1.02、1.01、1.04和1.05倍。这表明miR-126在CCD-18 Co肌成纤维细胞中来自红葡萄酒的多酚的抗炎特性中的潜在作用。
Chronic intestinal inflammation is an established risk factor for colon cancer. Polyphenolic compounds from fruit and vegetables have been shown to have anti-inflammatory properties in several cell lines and tissues. However, their anti-inflammatory mechanisms, involving microRNAs in the regulation of inflammation, have not been extensively investigated. The goal of this research was to assess the chemopreventive potential of polyphenolics extracted from red wine made with Lenoir grapes (Vitis aestivalis hybrid) in human colon-derived CCD-18Co myofibroblasts cells, and to assess the potential involvement of microRNA-126 (miR-126) in the underlying mechanisms. The results show that the polyphenolic red wine extract (WE) decreased mRNA expression of lipopolysaccharide (LPS)-induced inflammatory mediators NF-kB, ICAM-1, VCAM-1, and PECAM-1 by 1.95-, 1.98-, 1.52-, and 1.84-fold respectively, in a dose dependent manner (0-100 mu g of gallic acid equivalent (GAE) mL(-1)) down to 0.80-, 0.79-, 0.66-, and 0.68-fold in DMSO-treated control cells not challenged with LPS, respectively. Correspondingly, miR-126, which has a target region within the 3'-UTR of VCAM-1 mRNA, was increased 2.79-fold by the WE at 100 mu g GAE mL(-1). The potential role of miR-126 was confirmed by transfecting cells with a specific miR-126-antagomir, as-miR-126. Transfection with as-miR-126 down-regulated miR-126 to 0.71-fold in the control cells and up-regulated mRNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 to 1.80-, 1.49-, 2.30-, and 1.95-fold of controls, respectively. WE at 100 mu g GAE mL(-1) partially reversed the effects of the as-miR-126 to 1.02-, 1.01-, 1.04-, and 1.05-fold, form RNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 respectively. This indicates the potential role of miR-126 in the anti-inflammatory properties of polyphenolics from red wine in CCD-18Co myofibroblasts cells.