Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has an extremely poor prognosis. The major risk factors are chronic infection with hepatitis B viruses(HBV) as well as dietary exposure to aflatoxins. Prospective epidemiological studies have shown that there is a synergic interaction between HBV and aflatoxins in terms of HCC risk. However, the biology underlying this interaction is not fully understood. Midkine has mitogenic, antiapoptotic function in cancerogenesis and is also one of the inflammatory mediators. In this study, we aimed to evaluate underlying mechanisms of role of HBV infection in liver immune responses to carcinogenic/toxic substance aflatoxin B1. HBV infected(Hep3B) and noninfected(HepG2) human hepatocellularcancer cells cocultured with monocytic cells(THP-1) and are exposed to aflatoxin B1 for 24 h. Inflammatory responses of each cells defined with NFkB activation, IkB, TNF-a, IL-10, IFN-g and midkine secretion levels. Toll Like Receptor (TLRs) expression levels are evaluated by western blot. Exposure to aflatoxin results in activation of NFkB. The activation was higher in HBV infected group. HBV infection inhibits IFN-g secretion responses to aflatoxin in hepatocytes. TLR expression increased in cocultured hepatocytes in normal and aflatoxin exposed group. We found an increased inflammatory response that could be associated with the hepatotoxic effects of aflatoxin B1 in hepatocytes and monocytes. The predisposition of HBV-infected hepatocytes to aflatoxin-induced inflammatory damage is higher than non-infected hepatocytes. HBV infection supresses immune responses via inhibiting IFN-g production in liver cells. The increase in midkine secretion might be one of the underlying mechanisms of HBV induced carcinogenesis in aflatoxin exposure.

This study was supported by Ankara University.