Kanamori Yohei, Murakami Masaru, Sugiyama Makoto, Hashimoto Osamu, Matsui Tohru, Funaba Masayuki
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, Japan.
Vitam Horm. 2019;110:143-156. doi: 10.1016/bs.vh.2019.01.007. Epub 2019 Feb 2.
Hepcidin expression is determined through transcriptional regulation by systemic iron status. However, acute or chronic inflammation also increases the expression of hepcidin, which is associated with the dysregulation of iron metabolism in pathological conditions. Interleukin (IL)-6 has been suggested to be a principal molecule to confer inflammation-related hepcidin transcription, which is mediated via signal transducer and activator of transcription (STAT)-binding site on the hepcidin promoter. Recently, it has been uncovered that another pro-inflammatory cytokine IL-1β stimulates hepcidin expression through the distinct mechanism underlying IL-6-mediated hepcidin transcription. In addition to IL-6 induction, IL-1β stimulates expression of CCAAT-enhancer-binding protein (C/EBP)δ, a transcription factor, leading to transcriptional activation of hepcidin via C/EBP-binding site on the hepcidin promoter. Thus, hepcidin transcription is stimulated through multiple elements in response to proinflammatory cytokines. Relationships between increased production of IL-1β and dysregulated iron metabolism have been suggested in various diseases, which may be linked to overproduction of hepcidin.
铁调素的表达由全身铁状态通过转录调控来决定。然而，急性或慢性炎症也会增加铁调素的表达，这与病理状态下铁代谢失调有关。白细胞介素（IL）-6被认为是赋予炎症相关铁调素转录的主要分子，其通过铁调素启动子上的信号转导和转录激活因子（STAT）结合位点介导。最近，人们发现另一种促炎细胞因子IL-1β通过与IL-6介导的铁调素转录不同的机制刺激铁调素表达。除了诱导IL-6外，IL-1β还刺激转录因子CCAAT增强子结合蛋白（C/EBP）δ的表达，从而通过铁调素启动子上的C/EBP结合位点导致铁调素的转录激活。因此，铁调素转录通过多种元件响应促炎细胞因子而被刺激。在各种疾病中，已表明IL-1β产生增加与铁代谢失调之间的关系，这可能与铁调素的过度产生有关。
