Regulation and Function of Nitric Oxide in the Liver

The inducible nitric oxide synthase (iNOS) gene is expressed in nearly every organ and cell type during endotoxemia. Previously, we have shown that a combination of cytokines synergistically activate iNOS expression in the liver, and we have cloned the first human iNOS gene from cytokine-stimulated hepatocytes. We have also shown that steriods, TGF-β, the heat shock response, and nitric oxide (NO) itself, all down-regulate iNOS expression. In vivo, we have shown that hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury.