Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation.
BACKGROUND
Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial activation of human leukocytes.


METHODS
For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 mM), PC (0.38 mM), pooled human bile (2%) in combination with ethanol (0 to 66 mM).


RESULTS
Ethanol decreased integrity of intestinal epithelial cell monolayer and enhanced transepithelial permeability of endotoxin. Both the transepithelial permeability of endotoxin and the transepithelial stimulation of leukocytes were nearly completely abolished after the apical supplementation of PC with CPBS, but not by CPBS alone. Ethanol up to 66 mM was not able to reverse this effect.


CONCLUSIONS
A considerable part of the therapeutic and preventive effect of PC supplementation in ALD might result from a reduction of ethanol-enhanced permeability of endotoxin through the intestinal barrier.
Mitzscherling
Katja
K
Department Physiology of Nutrition, Institute for Nutritional Medicine, Hohenheim University, Stuttgart, Germany.
Volynets
Valentina
V
Parlesak
Alexandr
A
D001647:Bile Acids and Salts / Q000494:pharmacology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008070:Lipopolysaccharides / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002492:Central Nervous System Depressants; D016207:Cytokines; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D000431:Ethanol