Induction of nitric oxide synthase and subsequent production of nitric oxide not involved in interferon-gamma-induced hyperpermeability of Caco-2 intestinal epithelial monolayers.

Abstract

Caco-2 cell monolayers exposed to 1000 U/ml interferon-gamma (IFN-gamma) for 6 days elicited inducible nitric oxide synthase (iNOS) expression and increased translayer permeability. This iNOS increase was blocked by pyrrolidinedithiocarbamate (an inhibitor of iNOS induction) but it did not suppress the hyperpermeability response. Furthermore, 2,2'-(hydroxynitrosohydrazino) bis-ethanamine (a NO donor) did not increase monolayer permeability. Therefore, IFN-gamma-induced hyperpermeability is not due to its induction of iNOS activity and resulting increases in NO levels.