Inducible nitric oxide synthase is critical for immune-mediated liver injury in mice.

ABSTRACT: Concanavalin A (Con A) causes severe TNF-alpha-mediated and IFN-gamma-mediated liver injury in mice. In addition to their other functions, TNF-alpha and IFN-gamma both induce the inducible nitric oxide (NO) synthase (iNOS). Using different models of liver injury, NO was found to either mediate or prevent liver damage. To further elucidate the relevance of NO for liver damage we investigated the role of iNOS-derived NO in the Con A model. We report that iNOS mRNA was induced in livers of Con A-treated mice within 2 hours, with iNOS protein becoming detectable in hepatocytes as well as in Kupffer cells within 4 hours. iNOS-/- mice were protected from liver damage after Con A treatment, as well as in another TNF-alpha-mediated model that is inducible by LPS in D-galactosamine-sensitized (GalN

SUBMITTER: Sass G 

PROVIDER: S-EPMC199245 | biostudies-literature | 2001 Feb

REPOSITORIES: biostudies-literature