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Prepublished online as a Blood First Edition Paper on January 9, 2003; DOI 10.1182/blood-2002-08-2459. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2459v1 101/10/4148    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 Ludwiczek, S. Articles by Weiss, G. Search for Related Content PubMed PubMed Citation Articles by Ludwiczek, S. Articles by Weiss, G. Related Collections Phagocytes Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 4148-4154 PHAGOCYTES Cytokine-mediated regulation of iron transport in human monocytic cells Susanne Ludwiczek, Elmar Aigner, Igor Theurl, and Günter Weiss From the Department of Internal Medicine, University Hospital, Innsbruck, Austria. Under chronic inflammatory conditions cytokines induce a diversion of iron traffic, leading to hypoferremia and retention of the metal within the reticuloendothelial system. However, the regulatory pathways underlying these disturbances of iron homeostasis are poorly understood. We investigated transferrin receptor (TfR)-dependent and -independent iron transport mechanisms in cytokine-stimulated human monocytic cell lines THP-1 and U937. Combined treatment of cells with interferon- (IFN-) and lipopolysaccharide (LPS) reduced TfR mRNA levels, surface expression, and iron uptake, and these effects were reversed by interleukin-10 (IL-10), thus stimulating TfR-mediated iron acquisition. IFN- and LPS dose-dependently increased the cellular expression of divalent metal transporter-1, a transmembrane transporter of ferrous iron, and stimulated the uptake of nontransferrin bound iron (NTBI) into cells. At the same time, IFN- and LPS down-regulated the expression of ferroportin mRNA, a putative iron exporter, and decreased iron release from monocytes. Preincubation with IL-10 partly counteracted these effects. Our results demonstrate that the proinflammatory stimuli IFN- and LPS increase the uptake of NTBI via stimulation of divalent metal transporter-1 expression and cause retention of the metal within monocytes by down-regulating ferroportin synthesis. Opposite, the anti-inflammatory cytokine IL-10 stimulates TfR-mediated iron uptake into activated monocytes. The regulation of iron transport by cytokines is a key mechanism in the pathogenesis of anemia of chronic disease and a promising target for therapeutic intervention. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Nairz, I. Theurl, A. Schroll, M. Theurl, G. Fritsche, E. Lindner, M. Seifert, M.-L. V. Crouch, K. Hantke, S. Akira, et al. Absence of functional Hfe protects mice from invasive Salmonella enterica Serovar Typhimurium infection via induction of lipocalin-2 Blood, October 22, 2009; 114(17): 3642 - 3651. [Abstract] [Full Text] [PDF] I. Theurl, E. Aigner, M. Theurl, M. Nairz, M. Seifert, A. Schroll, T. Sonnweber, L. Eberwein, D. R. Witcher, A. T. Murphy, et al. 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