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Upregulation of iron regulatory hormone hepcidin by interferon α
Author(s) -
Ichiki Kazuhiko,
Ikuta Katsuya,
Addo Lynda,
Tanaka Hiroki,
Sasaki Yusuke,
Shimonaka Yasushi,
Sasaki Katsunori,
Ito Satoshi,
Shindo Motohiro,
Ohtake Takaaki,
Fujiya Mikihiro,
Torimoto Yoshihiro,
Kohgo Yutaka
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12348
Subject(s) - hepcidin , downregulation and upregulation , ferroportin , lipocalin , spleen , erythropoiesis , interferon , endocrinology , medicine , stat protein , biology , immunology , stat3 , signal transduction , inflammation , biochemistry , gene , anemia
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. Methods Mouse IFN α was administered to mice, and serum, spleen, bone marrow, liver, and duodenum tissue samples were subsequently collected. The messenger RNA (m RNA ) and protein expression of genes involved in iron metabolism were then analyzed by real‐time reverse transcription–polymerase chain reaction, W estern blotting, and liquid chromatography‐tandem mass spectrometry. Immunofluorescence for ferroportin was also performed. Results Among the gene expressions analyzed, we found that the expression of hepcidin, an iron regulatory hormone produced in the liver, was highly upregulated after IFN α treatment. Serum hepcidin levels and hepcidin m RNA expression in the liver were both found to be increased in the IFN α‐treated mice. The expression of ferroportin (the target molecule of hepcidin) in the duodenum of the IFN α‐treated mice was observed to be decreased, indicating that hepcidin upregulation could be physiologically functional. In vitro analysis of primary hepatocytes treated with IFN α and human hepatoma‐derived cells showed an upregulation of hepcidin m RNA , including an activation of signal transducer and activator of transcription3, which was shown to be involved in the hepcidin upregulation. Conclusions 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 .