Abstract
IntroductionThe intestinal epithelial barrier plays a critical role in host defense against luminal pathogens. Ethanol (EtOH) and dietary components may alter barrier integrity resulting in increased intestinal permeability, endotoxemia and multi‐organ pathology. The aim of the present study was to evaluate the effects of EtOH, linoleic acid (LA, a major unsaturated fatty acid in the Western diet), and its bioactive oxidized metabolites (OXLAMs) on Caco‐2 cells, an in vitro model of intestinal epithelial barrier.Materials and MethodsCaco‐2 cell monolayers were exposed to LA, OXLAMs (9‐and 13‐hydroxyoctadecadienoic acids, HODEs) and/or EtOH. Transepithelial resistance (TEER), expression of intestinal tight junction (TJ) proteins, and pro‐inflammatory response were evaluated.ResultsDecreased TEER in response to EtOH, LA, and multiple HODE isoforms was observed after 24 hours of exposure. Combined effects of EtOH and 13(S)HODE or +13HODE on TEER were greater compared to EtOH and 9(S)HODE or +9HODE. The combination of EtOH and 13(S)HODE or +13HODE resulted in greater down‐regulation of TJ proteins and increased expression of TNF‐α, IL‐1β, and IL‐6 mRNA compared to EtOH alone.ConclusionCombined exposure of EtOH and OXLAMs exacerbates disruption of intestinal barrier integrity and pro‐inflammatory response in Caco‐2 cells.
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