Epidermal growth factor inhibits cytokine-dependent nitric oxide synthase expression in hepatocytes

Liver cells express a wide range of extracellular receptors involved in the control of cell growth and arrest that can be studied ex vivo. Incubation of primary cultures of hepatocytes with IL-1 beta, TNF-alpha or lipopolysaccharide promotes the expression of the inducible form of nitric oxide synthase and NO release, a process that is inhibited to a different extent by incubation of the cells with EGF. In addition to this growth factor, IL-6 and TGF-beta also inhibited NO synthesis. Therefore, EGF by itself or in combination with other cytokines may be involved in the down-regulation of the NO synthesis that occurs in the early steps of liver regeneration.