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Blood, 1 January 2007, Vol. 109, No. 1, pp. 353-358. Prepublished online as a Blood First Edition Paper on August 31, 2006; DOI 10.1182/blood-2006-07-033969. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-033969v1 109/1/353    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Verga Falzacappa, M. V. Articles by Muckenthaler, M. U. Search for Related Content PubMed PubMed Citation Articles by Verga Falzacappa, M. V. Articles by Muckenthaler, M. U. Related Collections Red Cells Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation Maria Vittoria Verga Falzacappa1,2, Maja Vujic Spasic1,2, Regina Kessler2, Jens Stolte3, Matthias W. Hentze1,3,, and Martina U. Muckenthaler1,2, 1 Molecular Medicine Partnership Unit; 2 Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany; and 3 European Molecular Biology Laboratory, Heidelberg, Germany Hepcidin is a key iron-regulatory hormone produced by the liver. Inappropriately low hepcidin levels cause iron overload, while increased hepcidin expression plays an important role in the anemia of inflammation (AI) by restricting intestinal iron absorption and macrophage iron release. Its expression is modulated in response to body iron stores, hypoxia, and inflammatory and infectious stimuli involving at least in part cytokines secreted by macrophages. In this study we established and characterized IL6-mediated hepcidin activation in the human liver cell line Huh7. We show that the proximal 165 bp of the hepcidin promoter is critical for hepcidin activation in response to exogenously administered IL6 or to conditioned medium from the monocyte/macrophage cell line THP-1. Importantly, we show that hepcidin activation by these stimuli requires a STAT3 binding motif located at position –64/–72 of the promoter. The same STAT binding site is also required for high basal-level hepcidin mRNA expression under control culture conditions, and siRNA-mediated RNA knockdown of STAT3 strongly reduces hepcidin mRNA expression. These results identify a missing link in the acute-phase activation of hepcidin and establish STAT3 as a key effector of baseline hepcidin expression and during inflammatory conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Marques, A. M. Falcao, J. C. Sousa, G. Coppola, D. Geschwind, N. Sousa, M. Correia-Neves, and J. A. Palha Altered Iron Metabolism Is Part of the Choroid Plexus Response to Peripheral Inflammation Endocrinology, June 1, 2009; 150(6): 2822 - 2828. [Abstract] [Full Text] [PDF] P. Matak, T. B. Chaston, B. Chung, S. K. Srai, A. T. McKie, and P. A. Sharp Activated macrophages induce hepcidin expression in HuH7 hepatoma cells Haematologica, June 1, 2009; 94(6): 773 - 780. [Abstract] [Full Text] [PDF] H. Huang, M. Constante, A. Layoun, and M. M. 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[Abstract] [Full Text] [PDF] B. Chung, P. Matak, A. T. McKie, and P. Sharp Leptin Increases the Expression of the Iron Regulatory Hormone Hepcidin in HuH7 Human Hepatoma Cells J. Nutr., November 1, 2007; 137(11): 2366 - 2370. [Abstract] [Full Text] [PDF] J. Truksa, P. Lee, H. Peng, J. Flanagan, and E. Beutler The distal location of the iron responsive region of the hepcidin promoter Blood, November 1, 2007; 110(9): 3436 - 3437. [Abstract] [Full Text] [PDF] L. Valenti, E. A. Pulixi, P. Arosio, L. Cremonesi, G. Biasiotto, P. Dongiovanni, M. Maggioni, S. Fargion, and A. L. Fracanzani Relative contribution of iron genes, dysmetabolism and hepatitis C virus (HCV) in the pathogenesis of altered iron regulation in HCV chronic hepatitis Haematologica, August 1, 2007; 92(8): 1037 - 1042. [Abstract] [Full Text] [PDF]

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