Upregulation of iron regulatory hormone hepcidin by interferon α
- Disclosure: The authors have declared no conflict of interest.
Background and Aim
Interferon (IFN) activates various immune systems in vivo and is administered to patients with diseases such as viral hepatitis B, C, and malignant tumors. Iron dysregulation has been reported during treatment with IFN; however, it remains unclear whether IFN itself affects iron metabolism. We therefore determined the effect of IFN on iron metabolism.
Mouse IFNα was administered to mice, and serum, spleen, bone marrow, liver, and duodenum tissue samples were subsequently collected. The messenger RNA (mRNA) and protein expression of genes involved in iron metabolism were then analyzed by real-time reverse transcription–polymerase chain reaction, Western blotting, and liquid chromatography-tandem mass spectrometry. Immunofluorescence for ferroportin was also performed.
Among the gene expressions analyzed, we found that the expression of hepcidin, an iron regulatory hormone produced in the liver, was highly upregulated after IFNα treatment. Serum hepcidin levels and hepcidin mRNA expression in the liver were both found to be increased in the IFNα-treated mice. The expression of ferroportin (the target molecule of hepcidin) in the duodenum of the IFNα-treated mice was observed to be decreased, indicating that hepcidin upregulation could be physiologically functional. In vitro analysis of primary hepatocytes treated with IFNα and human hepatoma-derived cells showed an upregulation of hepcidin mRNA, including an activation of signal transducer and activator of transcription3, which was shown to be involved in the hepcidin upregulation.
Results indicate that iron absorption is decreased during IFN treatment; this favorable effect could inhibit iron overload during IFN treatment and may enhance the action of IFN.