Altered paracellular permeability in intestinal cell monolayer challenged with lipopolysaccharide: Modulatory effects of pterostilbene metabolites.

Gabriele Serreli, Maria Paola Melis, Sonia Zodio, Micaela Rita Naitza, Emanuela Casula, Pablo Peñalver, Ricardo Lucas, Roberto Loi, Juan Carlos Morales, Monica Deiana

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2020 Nov

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Epithelial barrier alteration is a central event in the pathogenesis of inflammatory bowel diseases. Lipopolysaccharide, correlated to the pathogenesis of such pathologies, has been demonstrated to cause altered membrane permeability, through the disruption and/or relocation of tight junction proteins, following redox-sensitive mitogen-activated protein kinases (MAPKs) modulation. Pterostilbene and its metabolite pinostilbene are natural stilbenoids which may reach relevant concentrations at intestinal level, together with their glucuronide and sulfate metabolites. The aim of our study was to evaluate the ability of these compounds to inhibit lipopolysaccharide-induced toxic effects on intestinal cell monolayer integrity and to explore the mechanism of action. Caco-2 cells, differentiated as enterocytes, were treated with lipopolysaccharide following pretreatment with the phenolic compounds at 1 μM physiological concentration. Caco-2 monolayer's permeability was monitored with time, measuring the transepithelial electrical resistance. Tight junction proteins were assessed by western blotting and immunofluorescence in lipopolysaccharide-treated cells, in relation to MAPK p38 and ERK1/2 activation. Pretreatment with all the phenolic compounds significantly slowed lipopolysaccharide-induced transepithelial electrical resistance decrease, preserved tight junction proteins levels and reduced MAPKs phosphorylation. The reported findings indicate that pterostilbene and its metabolites may counteract lipopolysaccharide-induced alteration of epithelial permeability, one of the initial events in the intestinal inflammatory process. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Gabriele Serreli, Maria Paola Melis, Sonia Zodio, Micaela Rita Naitza, Emanuela Casula, Pablo Peñalver, Ricardo Lucas, Roberto Loi, Juan Carlos Morales, Monica Deiana. Altered paracellular permeability in intestinal cell monolayer challenged with lipopolysaccharide: Modulatory effects of pterostilbene metabolites. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2020 Nov;145:111729