Resveratrol decreases TNFα-induced ICAM-1 expression and release by Sirt-1-independent mechanism in intestinal myofibroblasts

• Published in: Experimental cell research 2019-09, Vol.382 (2), p.111479-111479, Article 111479
• Main Authors: Domazetovic, Vladana, Bonanomi, Andrea Giovanni, Stio, Maria, Vincenzini, Maria Teresa, Iantomasi, Teresa
• Format: Article
• Language: English
• Subjects: ICAM-1; IκB-α; NF-κB; Resveratrol; Sirtuin-1; TNFα
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2019.06.024

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. •Resveratrol (RE) reduces TNFα-induced up-regulation of ICAM-1 expression and release.•The mechanism involved in this RE effect is redox-regulated and Sirt-1-independent.•RE down-regulates ICAM-1 levels by reducing ROS and IκB-α degradation.•NF-κB is not the only factor involved in TNFα-induced ICAM-1 up-regulation.