Nitric oxide mediates interferon-gamma-induced hyperpermeability in cultured human intestinal epithelial monolayers

Critical Care Medicine
N UnnoM P Fink

Abstract

Incubation with interferon-gamma has been shown to increase the permeability of cultured monolayers of intestinal epithelial cells. We sought to determine whether this phenomenon is mediated, at least in part, by increased production of nitric oxide. Prospective, controlled, laboratory study. Human intestinal epithelial (Caco-2BBe) cells were grown as monolayers on permeable supports mounted in bicameral chambers. Permeability was assessed by adding fluorescein sulfonic acid (molecular weight = 478 daltons) to the apical compartment and determining the apical-to-basolateral clearance of the probe over a 24-hr period of incubation. Basic science laboratory. The permeability of monolayers to fluorescein sulfonic acid was significantly increased after incubation in the presence of interferon-gamma (250 to 1000 U/mL). The effect of interferon-gamma on permeability was dependent on both the concentration of the cytokine and the duration of exposure to it. Concentrations of nitric oxide oxidation products, nitrite and nitrate, in incubation media were increased after exposure of cells to interferon-gamma. When intestinal epithelial (Caco-2BBe) monolayers were incubated with interferon-gamma in the presence of inhibitors of nitric oxi...Continue Reading

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