Interferon gamma promotes chemically induced apoptosis in primary hepatocytes by inducing p53 accumulation

Interferon gamma has been implicated in different inflammatory processes within the liver. Besides its well studied role in the regulation of the immune response little is known so far about the direct effects of interferon gamma on hepatocytes. The aim of the study was, therefore, to see whether interferon gamma has any effects on survival or proliferation of primary mouse hepatocytes.

We found that stimulation of hepatocytes resulted in an activation of Stat–1 signaling indicating a functional interferon-gamma receptor on hepatocytes. Nevertheless, survival or proliferation was unaltered. However, interferon gamma in combination with genotoxic stress induced by cisplatin markedly increased hepatocellular death, indicating that interferon gamma may promote apoptosis. Enhanced apoptosis could be explained by interferon induced accumulation of p53. This accumulation was not associated with p53 activation, as indicated by the lack of p21 expression; activation of p53 required additional DNA-damage by cisplatin.

In conclusion, interferon gamma primes hepatocytes for apoptosis by inducing p53 accumulation. Thus, interferon gamma exposed hepatocytes respond more readily to DNA-damage with apoptosis. Therefore, interferon gamma may prevent the accumulation of DNA-damage and carcinogenesis in inflammed tissue.

interferon apoptosis