SEARCH:   Advanced

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: 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. Santos Contribution of STAT3 and SMAD4 pathways to the regulation of hepcidin by opposing stimuli Blood, April 9, 2009; 113(15): 3593 - 3599. [Abstract] [Full Text] [PDF] J. Truksa, P. Lee, and E. Beutler Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness Blood, January 15, 2009; 113(3): 688 - 695. [Abstract] [Full Text] [PDF] J. F. Collins, M. Wessling-Resnick, and M. D. Knutson Hepcidin Regulation of Iron Transport J. Nutr., November 1, 2008; 138(11): 2284 - 2288. [Abstract] [Full Text] [PDF] C. Camaschella and L. Silvestri New and old players in the hepcidin pathway Haematologica, October 1, 2008; 93(10): 1441 - 1444. [Full Text] [PDF] P. N. Paradkar, I. De Domenico, N. Durchfort, I. Zohn, J. Kaplan, and D. M. Ward Iron depletion limits intracellular bacterial growth in macrophages Blood, August 1, 2008; 112(3): 866 - 874. [Abstract] [Full Text] [PDF] N. C. Andrews Forging a field: the golden age of iron biology Blood, July 15, 2008; 112(2): 219 - 230. [Full Text] [PDF] I. Theurl, M. Theurl, M. Seifert, S. Mair, M. Nairz, H. Rumpold, H. Zoller, R. Bellmann-Weiler, H. Niederegger, H. Talasz, et al. Autocrine formation of hepcidin induces iron retention in human monocytes Blood, February 15, 2008; 111(4): 2392 - 2399. [Abstract] [Full Text] [PDF] E. H.J.M. Kemna, H. Tjalsma, H. L. Willems, and D. W. Swinkels Hepcidin: from discovery to differential diagnosis Haematologica, January 1, 2008; 93(1): 90 - 97. [Abstract] [Full Text] [PDF] M. D. Fleming The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism Hematology, January 1, 2008; 2008(1): 151 - 158. [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]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020