No abstract

TNF tolerance towards GalN/TNF treatment is mediated by TNFR-1. IL-1beta, iNOS and HO-1 neither mediated TNF-tolerance nor TNF cytotoxicity.

Inducible nitric oxide synthase (iNOS) has been shown to play an important role in the development of liver injury. iNOS deficiency protects mice from hemorrhage/resuscitation as well as from cytokine-mediated liver injury, for example, after administration of concanavalin A (con A). Here we investigated the in vivo effects of tumor necrosis factor (TNF)-␣ and/or interferon (IFN)-␥, two mediators of con A-induced liver injury, the TNF receptor (TNFR) usage leading to iNOS expression, and its connection with nuclear factor B (NF-B) activation. In conclusion, iNOS expression in vivo is dependent on both TNF-␣ and IFN-␥. Although con A-induced liver injury depends on both TNFR1 and TNFR2, TNF-dependent iNOS expression is mediated exclusively by TNFR1 and requires NF-B activation. (HEPATOLOGY