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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2392-2399. Prepublished online as a Blood First Edition Paper on December 11, 2007; DOI 10.1182/blood-2007-05-090019. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-090019v1 111/4/2392    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 Google Scholar Articles by Theurl, I. Articles by Weiss, G. PubMed PubMed Citation Articles by Theurl, I. Articles by Weiss, G. Related Collections Phagocytes Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Autocrine formation of hepcidin induces iron retention in human monocytes Igor Theurl1, Milan Theurl1, Markus Seifert1, Sabine Mair1, Manfred Nairz1, Holger Rumpold2, Heinz Zoller3, Rosa Bellmann-Weiler1, Harald Niederegger4, Heribert Talasz5, and Günter Weiss1 Departments of1 General Internal Medicine, 2 Hematology and Oncology, and 3 Gastroenterology and Hepatology, Medical University, Innsbruck; 4 Tyrolean Cancer Research Institute, Innsbruck; and 5 Biocenter, Division of Clinical Biochemistry, Medical University, Innsbruck, Austria Hepcidin, a master regulator of iron homeostasis, is produced in small amounts by inflammatory monocytes/macrophages. Chronic immune activation leads to iron retention within monocytes/macrophages and the development of anemia of chronic disease (ACD). We questioned whether monocyte-derived hepcidin exerts autocrine regulation toward cellular iron metabolism. Monocyte hepcidin mRNA expression was significantly induced within 3 hours after stimulation with LPS or IL-6, and hepcidin mRNA expression was significantly higher in monocytes of ACD patients than in controls. In ACD patients, monocyte hepcidin mRNA levels were significantly correlated to serum IL-6 concentrations, and increased monocyte hepcidin mRNA levels were associated with decreased expression of the iron exporter ferroportin and iron retention in these cells. Transient transfection experiments using a ferroportin/EmGFP fusion protein construct demonstrated that LPS inducible hepcidin expression in THP-1 monocytes resulted in internalization and degradation of ferroportin. Transfection of monocytes with siRNA directed against hepcidin almost fully reversed this lipopolysaccharide-mediated effect. Using ferroportin mutation constructs, we found that ferroportin is mainly targeted by hepcidin when expressed on the cell surface. Our results suggest that ferroportin expression in inflammatory monocytes is negatively affected by autocrine formation of hepcidin, thus contributing to iron sequestration within monocytes as found in ACD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Elucidating the role of monocyte-derived hepcidin Harish P. Janardhan Blood 2008 111: 3902. [Full Text] [PDF] This article has been cited by other articles: H. P. Janardhan Elucidating the role of monocyte-derived hepcidin Blood, April 1, 2008; 111(7): 3902 - 3902. [Full Text] [PDF] G. Weiss and I. Theurl Response: Monocyte hepcidin and the anemia of chronic disease Blood, April 1, 2008; 111(7): 3902 - 3903. [Full Text] [PDF]

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