Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

Alexandr Parlesak, Simone Schaeckeler, Lydia Moser, Christiane Bode

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    Abstract

    Objective: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent activation of basolaterally cocultured human mononuclear leukocytes was measured. Design: In a coculture model, a layer of differentiated, confluent Caco-2 cells was apically stimulated with growth-arrested, nonpathogenic Escherichia coli. Setting: Basic human cell culture laboratory. Interventions: The effect of CPBS (0.5 mM and 1.5 mM), phosphatidylcholine(0.38 mM), and human bile (0.5% vol/vol) on the barrier function was assessed by the measurement of transepithelial electrical resistance, by endotoxin permeability through the intestinal epithelial cell layer, and by basolateral cytokine enzyme-linked immunosorbent assay measurement (tumor necrosis factor-alpha, interleukins-6, 8, and 10). Micelles formed by CPBS were detected by dynamic light scattering. The association of endotoxin with CPBS micelles was tested by fluorescence resonance energy transfer. Measurements and Main Results: Apical addition of CPBS suppressed the permeability of endotoxins through the intestinal epithelial cell layer significantly. In parallel, apical supplementation of CPBS dose-dependently reduced the basolateral production of all cytokines measured. Apical phosphatidylcholine supplementation enhanced this effect significantly. CPBS formed micelles (diameter, 134 +/- 7 nm), which were able to bind endotoxin to their surface. Conclusions: CPBS can reduce the permeation of endotoxin through intestinal epithelial cell layers by binding it to micelles. Thereby, the inflammatory processes beyond the mucosal surface are suppressed, an effect that is enhanced by phosphatidylcholine.
    Original languageEnglish
    JournalCritical Care Medicine
    Volume35
    Issue number10
    Pages (from-to)2367-74
    ISSN0342-4642
    DOIs
    Publication statusPublished - 2007

    Keywords

    • endotoxin
    • inflammation
    • bile
    • conjugated primary bile salts
    • intestinal epithelial cells
    • phosphatidylcholine

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