Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 490062
Title Ethanol Impairs Intestinal Barrier Function in Humans through Mitogen Activated Protein Kinase Signaling: A Combined In Vivo and In Vitro Approach
Author(s) Elamin, E.; Masclee, A.; Troost, F.; Pieters, H.J.; Keszthelyi, D.; Aleksa, K.; Dekker, J.; Jonkers, D.
Source PLoS ONE 9 (2014)9. - ISSN 1932-6203
Department(s) Department of Animal Sciences
Publication type Refereed Article in a scientific journal
Publication year 2014
Keyword(s) alcoholic liver-disease - caco-2 cell monolayer - paracellular permeability - actin cytoskeleton - aldehyde dehydrogenases - epithelial barrier - tight - disruption - consumption - metabolism
Abstract Background: Ethanol-induced gut barrier disruption is associated with several gastrointestinal and liver disorders. Aim: Since human data on effects of moderate ethanol consumption on intestinal barrier integrity and involved mechanisms are limited, the objectives of this study were to investigate effects of a single moderate ethanol dose on small and large intestinal permeability and to explore the role of mitogen activated protein kinase (MAPK) pathway as a primary signaling mechanism. Methods: Intestinal permeability was assessed in 12 healthy volunteers after intraduodenal administration of either placebo or 20 g ethanol in a randomised cross-over trial. Localization of the tight junction (TJ) and gene expression, phosphorylation of the MAPK isoforms p38, ERK and JNK as indicative of activation were analyzed in duodenal biopsies. The role of MAPK was further examined in vitro using Caco-2 monolayers. Results: Ethanol increased small and large intestinal permeability, paralleled by redistribution of ZO-1 and occludin, downregulation of ZO-1 and up-regulation of myosin light chain kinase (MLCK) mRNA expression, and increased MAPK isoforms phosphorylation. In Caco-2 monolayers, ethanol increased permeability, induced redistribution of the junctional proteins and F-actin, and MAPK and MLCK activation, as indicated by phosphorylation of MAPK isoforms and myosin light chain (MLC), respectively, which could be reversed by pretreatment with either MAPK inhibitors or the anti-oxidant L-cysteine. Conclusions: Administration of moderate ethanol dosage can increase both small and colon permeability. Furthermore, the data indicate a pivotal role for MAPK and its crosstalk with MLCK in ethanol-induced intestinal barrier disruption.
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