Resveratrol improves TNF-alpha-induced endothelial dysfunction in a coculture model of a Caco-2 with an endothelial cell line


Toaldo I. M., Van Camp J., Gonzales G. B., Kamiloglu S., Bordignon-Luiz M. T., Smagghe G., ...More

JOURNAL OF NUTRITIONAL BIOCHEMISTRY, vol.36, pp.21-30, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36
  • Publication Date: 2016
  • Doi Number: 10.1016/j.jnutbio.2016.07.007
  • Journal Name: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.21-30
  • Keywords: Cardiovascular disease, Coculture, ICAM-1, Intestine, Nitric oxide, Resveratrol, NITRIC-OXIDE SYNTHASE, FACTOR-KAPPA-B, OXIDATIVE STRESS, GROWTH-FACTOR, EXPRESSION, CANCER, METABOLITES, ABSORPTION, NEOVASCULARIZATION, BIOAVAILABILITY
  • Bursa Uludag University Affiliated: No

Abstract

The bioactivity of trans-resveratrol (RSV), an important wine polyphenol, and of its metabolites was investigated in a more relevant setup comprising an in vitro coculture cell model that combines intestinal absorption and conjugation with changes in endothelial function, which is primarily affected in cardiovascular diseases. Caco-2 and endothelial EA.hy926 cells were grown in a coculture, and Caco-2 cells were treated with RSV in the coculture and in two different sequential setups for 4 h and 24 h. Transported metabolites were investigated by UPLC MS/MSE, and the effects on NO production, ROS inhibition and secretion of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-alpha-activated and nonactivated endothelial cells. RSV and four conjugated metabolites, two sulfates and two glucuronides, were identified after intestinal transport. In both coculture and sequential systems, RSV at 20 mu M strongly induced NO production. Changes in ROS and NO levels demonstrated a clear effect of crosstalk between cells in the coculture. The secretion of proinflammatory cytokines and VEGF was largely increased by treatment with TNF-alpha (inflammatory condition). The polyphenol intervention significantly reduced the levels of VEGF, ROS, IL-8 and ICAM-1, with a more pronounced effect in TNF-alpha-activated endothelial cells. In conclusion, RSV and its metabolites showed accentuated bioactivity on TNF-alpha-induced inflammation, and the metabolism of endothelial cells as a biological target was not only influenced by these phenolics but also by the communication between distinct cell lines, showing a new perspective for investigations on polyphenol intervention and its biological outcomes. (C) 2016 Elsevier Inc. All rights reserved.