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
Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
J Gastroenterol Hepatol. 2014 Feb;29(2):387-94. doi: 10.1111/jgh.12348.
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.
干扰素（IFN）可在体内激活多种免疫系统，被用于治疗乙型和丙型病毒性肝炎、恶性肿瘤等疾病。已有报道称在IFN治疗期间会出现铁调节异常；然而，IFN本身是否影响铁代谢仍不清楚。因此，我们确定了IFN对铁代谢的影响。
给小鼠注射小鼠IFNα，随后收集血清、脾脏、骨髓、肝脏和十二指肠组织样本。然后通过实时逆转录-聚合酶链反应、蛋白质免疫印迹法和液相色谱-串联质谱法分析参与铁代谢的基因的信使核糖核酸（mRNA）和蛋白质表达。还进行了铁转运蛋白的免疫荧光检测。
在分析的基因表达中，我们发现肝脏产生的铁调节激素铁调素的表达在IFNα治疗后高度上调。在IFNα治疗的小鼠中，血清铁调素水平和肝脏中铁调素mRNA表达均升高。观察到IFNα治疗的小鼠十二指肠中铁转运蛋白（铁调素的靶分子）的表达降低，表明铁调素上调可能具有生理功能。对用IFNα处理的原代肝细胞和人肝癌衍生细胞的体外分析显示铁调素mRNA上调，包括信号转导子和转录激活子3的激活，该因子被证明参与铁调素上调。
结果表明，IFN治疗期间铁吸收减少；这种有利作用可抑制IFN治疗期间的铁过载，并可能增强IFN的作用。
