Interleukin induces hepcidin expression through STAT3
Interleukin induces hepcidin expression through STAT3
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DOI：
10.1182/blood-2006-06-027631
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发表时间：
2006-11-01
期刊：
影响因子：
20.3
通讯作者：
Andrews, Nancy C.
中科院分区：
文献类型：
--
作者：
Wrighting, Diedra M.;Andrews, Nancy C.
铁的动态平衡是通过严格调节循环中的海普西丁水平来维持的。海普西丁水平过低或过高分别会导致铁超载或缺铁。虽然已知缺氧、红系需求、铁和炎症都会影响海普西丁的表达，但其机制尚未明确。在这篇报道中，我们展示了炎性细胞因子白介素6(IL-6)通过诱导和随后的信号转导和转录激活子3(STAT3)的启动子结合来直接调节海普西丁。STAT3对于海普西丁启动子的IL-6反应是必要和充分的。我们的发现提供了一种机制，即海普西丁可以通过炎症来调节，或者在没有炎症刺激的情况下，通过导致STAT3激活的替代机制来调节。
Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation.