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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 11, 2006 Accepted August 9, 2006 STAT-3 mediates hepatic hepcidin expression and its inflammatory stimulation Maria Vittoria Verga Falzacappa, Maja Vujic Spasic, Regina Kessler, Jens Stolte, Matthias W Hentze, and Martina U Muckenthaler* MMPU/Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany European Molecular Biology Laboratory, Heidelberg, Germany Molecular Medicine Partnership Unit/European Molecular Biology Laboratory, Heidelberg, Germany * Corresponding author; email: martina.muckenthaler{at}med.uni-heidelberg.de. 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 anaemia of inflammation (AI) by restricting intestinal iron absorption and macrophage iron release. Its expression is modulated in response to body iron stores, hypoxia, inflammatory and infectious stimuli, involving at least in part cytokines secreted by macrophages. In this study we established and characterized IL-6-mediated hepcidin activation in the human liver cell line Huh7. We show that the proximal 165bp of the hepcidin promoter are critical for hepcidin activation in response to exogenously administered IL-6 or to conditioned medium from the monocyte/macrophage cell line THP-1. Importantly, we show that hepcidin activation by these stimuli requires a STAT-3 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 knock-down of STAT-3 strongly reduces hepcidin mRNA expression. These results identify a missing link in the acute phase activation of hepcidin and establish STAT-3 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: E. M. del Giudice, N. Santoro, A. Amato, C. Brienza, P. Calabro, E. T. Wiegerinck, G. Cirillo, N. Tartaglione, A. Grandone, D. W. Swinkels, et al. Hepcidin in Obese Children as a Potential Mediator of the Association between Obesity and Iron Deficiency J. Clin. Endocrinol. Metab., December 1, 2009; 94(12): 5102 - 5107. [Abstract] [Full Text] [PDF] C. L. Koening, J. C. Miller, J. M. Nelson, D. M. Ward, J. P. Kushner, L. K. Bockenstedt, J. J. Weis, J. Kaplan, and I. De Domenico Toll-like receptors mediate induction of hepcidin in mice infected with Borrelia burgdorferi Blood, August 27, 2009; 114(9): 1913 - 1918. [Abstract] [Full Text] [PDF] C. Vecchi, G. Montosi, K. Zhang, I. Lamberti, S. A. Duncan, R. J. Kaufman, and A. Pietrangelo ER Stress Controls Iron Metabolism Through Induction of Hepcidin Science, August 14, 2009; 325(5942): 877 - 880. [Abstract] [Full Text] [PDF] 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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