HGF‐mediated control of IL‐6 production in primary rat hepatocyte cultures

Abstract

Hepatocyte Growth Factor (HGF) is an omnipotent growth factor that targets various kinds of cells. As an extracellular signal, HGF is able to trigger many downstream signaling pathways through its receptor, MET. One such pathway involves the transcription factor, NF-kappaB. We report here that two different concentrations of HGF (20ng/ml, growth-promoting; 500 ng/ml, growth-suppressing) in serum-free rat hepatocyte cultures generate different responses of both NF-kappaB and its regulated gene product, interleukin-6 (IL-6). The low dose of HGF leads to translocation of the NF-kappaB complex (p50/p65) to the hepatocellular nucleus whereas; the high dose has the opposite effect, blocking the complex in the cytoplasm. Transcription of the well-known downstream target of macrophage NF-kappaB, IL-6, mimicked these results. Surprisingly, immuno-staining showed that the transcriptional results were reflected at the protein level in hepatocytes, i.e. the IL-6 staining was hepatocellular and changed with the concentration of HGF. These findings emphasize the importance of HGF concentration effects and reveal what may be a previously undisclosed biological role for IL-6 in hepatocyte cultures.