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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3204-3209.
Prepublished online as a Blood First Edition Paper on July 11, 2006; DOI 10.1182/blood-2006-06-027631.
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RED CELLS
Interleukin-6 induces hepcidin expression through STAT3
Diedra M. Wrighting, and
Nancy C. Andrews
From the graduate program in Biological and Biomedical Sciences, Harvard University, Boston, MA; the Division of Hematology/Oncology, Children's Hospital Boston and the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; and the Howard Hughes Medical Institute, Chevy Chase, MD.
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.

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