Regulation of hepcidin expression in HepG2 cells

Background & Aims: The hepatic peptide hepcidin is proposed to be a central regulator of iron homeostasis. Hepcidin acts as negative regulator of intestinal iron absorption and of iron release from macrophages. It also exhibits antimicrobial acvtivity as a type II acute-phase reactant. We have analysed the regulation of hepcidin expression in the human hepatoma cell line, HepG2 cells, by iron, deferoxamine (DFO), interleukin–6 (IL–6), lipopolysaccaride (LPS), and ethanol. Methods: Hepcidin mRNA expression was shown by RT-PCR experiments. Specific hepcidin antibodies were raised against N-terminal and C-terminal epitopes of the propeptide to study hepcidin expression by immunoblot analyses on the protein level. Results: Hepcidin was expressed in HepG2 cells. It was significantly upregulated by iron, IL–6 and LPS. A downregulation of hepcidin expression was observed by DFO and by ethanol in HepG2 cells transfected with alcohol dehydrogenase. Interestingly, IL–6 abolished the effect of ethanol metabolism on hepcidin expression. Conclusions: Our findings suggest that the type II acute-phase peptide hepcidin provides a molecular link between inflammation, resulting anemia, and the regulation of iron metabolism. The downregulation of hepcidin by ethanol explains the hepatic iron overload as observed in alcoholic liver disease.

Keywords: Hepcidin, iron metabolism, liver