(-)-Epicatechin in the prevention of tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity

Telma C. Contreras, Elisabetta Ricciardi, Eleonora Cremonini, Patricia I. Oteiza

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of inflammatory bowel diseases (IBD). Tumor necrosis alpha (TNFα) plays a central role in IBD pathogenesis, in part promoting tight function (TJ) barrier dysfunction. Food extracts enriched in (-)-epicatechin (EC) prevent the development or improve the progression of IBD in animal models. This study investigated the capacity of EC to inhibit TNFα-induced permeabilization of Caco-2 cell monolayers, characterizing the underlying mechanisms. Caco-2 cells differentiated into intestinal epithelial cells were incubated in the absence/presence of TNFα, with or without the addition of 0.5-5 μM EC. TNFα triggered cell monolayer permeabilization, decreasing transepithelial electrical resistance (TEER) and increasing the paracellular transport of fluorescein sulfonic acid. The permeabilizing effects of TNFα were not due to Caco-2 cell apoptosis as evaluated by DNA fragmentation, caspase 3 and 9 activation, and cell morphology. EC prevented TNFα-triggered Caco-2 monolayer permeabilization and acted inhibiting the associated: (i) NADPH oxidase (NOX)-mediated increased oxidant production, (ii) NF-κB (IκBα phosphorylation, p50 and RelA nuclear transport, and nuclear NF-κB-DNA binding) and ERK1/2 activation, (iii) increased myosin light kinase expression, and decreased TJ protein ZO-1 levels. In summary, EC prevented TNFα-mediated Caco-2 cell barrier permeabilization in part through the inhibition of NOX/NF-κB activation and downstream TJ disruption. Diets rich in EC could contribute to ameliorate IBD-associated increased intestinal permeability.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume573
DOIs
StatePublished - May 1 2015

Keywords

  • (-)-Epicatechin
  • Inflammation
  • Intestinal barrier
  • Intestinal permeability
  • NADPH oxidase
  • Tight junction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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