TNF-driven inflammation during mouse liver regeneration after partial hepatectomy and its role in growth regulation of liver.

Abstract

To determine the role of TNF-driven inflammation in self-regulation of cell growth and differentiation, mouse liver regeneration after partial hepatectomy was examined for TNF-driven inflammation. Hepatectomy provoked priming state for TNF production in both whole body and liver on day 3 when the peak mitotic response occurred. Histochemical studies of liver also showed an inflammatory symptom; hepatocellular necrotic foci appeared by 6 hours after hepatectomy. TNF itself was secreted spontaneously in liver transiently on day 1 to 2 after hepatectomy just before the proliferation of hepatocytes. Dexamethasone reduced both TNF secretion and hepatocyte proliferation after hepatectomy. Recombinant murine TNF stimulated the in vitro proliferation of hepatocytes. These findings indicate that hepatectomy induces short-term secretion of TNF in liver and TNF-driven inflammation has an important role in liver regeneration, at least in part by the direct stimulation of hepatocyte proliferation.