Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 573, Issue -, Pages 84-91Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2015.01.024
Keywords
(-)-Epicatechin; NADPH oxidase; Intestinal barrier; Inflammation; Tight junction; Intestinal permeability
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Funding
- CHNR-State of California Vitamin Price Fixing Consumer Settlement Fund, NIFA-USDA [CA-D*-xxx-7244-H]
- University of California, Davis
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An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of inflammatory bowel diseases (IBD). Tumor necrosis alpha (TNE alpha) 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 TNF alpha-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 TNF alpha, with or without the addition of 0.5-5 mu M EC. TNF alpha triggered cell monolayer permeabilization, decreasing transepithelial electrical resistance (TEER) and increasing the paracellular transport of fluorescein sulfonic acid. The permeabilizing effects of TNF alpha were not due to Caco-2 cell apoptosis as evaluated by DNA fragmentation, caspase 3 and 9 activation, and cell morphology. EC prevented TNF alpha-triggered Caco-2 monolayer permeabilization and acted inhibiting the associated: (i) NADPH oxidase (NOX)-mediated increased oxidant production, (ii) NF-kappa B (I kappa B alpha, phosphorylation, p50 and RelA nuclear transport, and nuclear NF-kappa B-DNA binding) and ERK1/2 activation, (iii) increased myosin light kinase expression, and decreased TJ protein ZO-1 levels. In summary, EC prevented TNF alpha-mediated Caco-2 cell barrier permeabilization in part through the inhibition of NOX/NF-kappa B activation and downstream TJ disruption. Diets rich in EC could contribute to ameliorate IBD-associated increased intestinal permeability. (C) 2015 Elsevier Inc. All rights reserved.
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