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

Abstract

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 upregulation 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.

The myofibroblast at a glance

“…Furthermore, junctional adhesion molecules (JAMs) exist between myofibroblasts and endothelial cells (Hintermann et al, 2016), together with the zonula occludens protein 1 (TJP1) in dermal fibroblasts (Morris et al, 2006). Finally, the cell-adhesion molecules (CAMs) ICAM1 and VCAM1 are expressed in subtypes of myofibroblast (Fontani et al, 2016;Hellerbrand et al, 1996), where they promote communication with immune cells, including T-cells (Bombara et al, 1993) and neutrophils (Clayton et al, 1997;Domazetovic et al, 2019). In addition to direct intercellular communication, myofibroblast transmission of force to fibrous ECM generates mechanical signals (see poster).…”

Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol

“…After removal of this medium MLO-Y4 cells were cultured for 24 and/or 48 h in complete medium or in starved medium in the presence or not of the inhibitors. The inhibitor concentrations used are those that induced the maximum inhibition without interfering with cellular viability [30,81].…”

Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

“…In fact, bis-δ-tocopheryl sulfide and disulfide, contrarily to α-Toc and δ-Toc, at both low and high concentrations, are able to completely prevent the increase of ROS levels and ICAM-1 expression increase, similarly to large excesses of NAC. These data indicate that in HT29 cells TNFα up-regulates the expression of ICAM-1 only by redox regulated mechanisms, differently to those verified in intestinal myofibroblasts, in which TNFα up-regulates ICAM-1 expression by both redox-dependent and-independent mechanisms [67,68]. On the other hand, both these mechanisms appear to be involved in the TNFα-induced up-regulation of Cl-2 expression that in HT29 cells is not directly related to ROS levels.…”