Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Viale Morgagni 50, 50134, Florence, Italy.
Gastroenterology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
Exp Cell Res. 2019 Sep 15;382(2):111479. doi: 10.1016/j.yexcr.2019.06.024. Epub 2019 Jun 21.
Up-regulation of intercellular adhesion molecule-1 (ICAM-1) and its soluble form are involved in the chronic inflammation. For the first time, we demonstrated that resveratrol (RE), a natural polyphenol with antioxidant and anti-inflammatory properties, reduces the increase of expression and release of ICAM-1, due to TNFα-induced oxidative stress, in a myofibroblast cell line derived from human colonic (18Co cells). RE is scavenger of radical oxygen species (ROS) and modulates signaling pathways in which Sirt-1 and NF-κB are involved. Effectively, in TNFα-stimulated 18Co cells RE decreases ROS production and increases Sirt-1 expression and activity, but it reduces TNFα-induced ICAM-1 up-regulation by a Sirt-1-independent mechanism, as demonstrated by EX527 and Sirt-1 siRNA treatments. RE inhibits TNFα-induced activation of NF-κB by reducing both ROS and the degradation of IκB-α, an endogenous inhibitor of NF-κB, with consequent decrease of NF-κB nuclear translocation. This study also shows that NF-κB is not the only factor involved in the TNFα-induced ICAM-1 up-regulation and confirms our previous evidence according to which TNFα increases ICAM-1 levels by redox- and non-redox-regulated mechanisms. RE can represent good and useful support in therapies for intestinal inflammatory diseases in which TNFα plays a crucial role in the increase of adhesion molecule expression.
细胞间黏附分子-1（ICAM-1）及其可溶性形式的上调与慢性炎症有关。我们首次证明，白藜芦醇（RE）是一种具有抗氧化和抗炎特性的天然多酚，可降低 TNFα 诱导的氧化应激导致的人结肠衍生的肌成纤维细胞系（18Co 细胞）中 ICAM-1 的表达和释放增加。RE 是自由基（ROS）的清除剂，并调节涉及 Sirt-1 和 NF-κB 的信号通路。实际上，在 TNFα 刺激的 18Co 细胞中，RE 减少 ROS 的产生并增加 Sirt-1 的表达和活性，但通过 Sirt-1 非依赖性机制降低 TNFα 诱导的 ICAM-1 上调，如通过 EX527 和 Sirt-1 siRNA 处理所示。RE 通过减少 ROS 和 NF-κB 的内源性抑制剂 IκB-α的降解来抑制 TNFα 诱导的 NF-κB 激活，从而导致 NF-κB 核易位减少。这项研究还表明，NF-κB 并不是 TNFα 诱导的 ICAM-1 上调所涉及的唯一因素，并证实了我们之前的证据，即 TNFα 通过氧化还原和非氧化还原调节机制增加 ICAM-1 水平。RE 可在 TNFα 在增加黏附分子表达中起关键作用的肠道炎症性疾病的治疗中提供良好且有用的支持。
