Cited by 197Iron Metabolism and DisordersTrace Elements in HealthImmune Response and Inflammation

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Regulation of Reticuloendothelial Iron Transporter MTP1 (Slc11a3) by Inflammation

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Yang, Funmei, Liu, Xiao-bing, Quinones, Marlon, Melby, Peter C., Ghio, Andrew, Haile, David J.·2002·Journal of Biological Chemistry

DOI 10.1074/jbc.m201485200

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Abstract

Acute and chronic inflammation cause many changes in total body iron metabolism including the sequestration of iron in phagocytic cells of the reticuloendothelial system. This change in iron metabolism contributes to the development of the anemia of inflammation. MTP1, the duodenal enterocyte basolateral iron exporter, is also expressed in the cells of the reticuloendothelial system (RES) and is likely to be involved in iron recycling of these cells. In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation. The down-regulation of splenic expression of MTP1 by inflammation was also observed in a Leishmania donovani model of chronic infection. The response of MTP1 to lipopolysaccharide (LPS) requires signaling through the LPS receptor, Toll-like receptor 4 (TLR4). In mice lacking TLR4, MTP1 expression is not altered in response to LPS. In addition, mice lacking tumor necrosis factor-receptor 1a respond appropriately to LPS with down-regulation of MTP1, despite hyporesponsiveness to tumor necrosis factor-alpha signaling, suggesting that this cytokine may not be required for the LPS effect. We hypothesize that the iron sequestration in the RES system that accompanies inflammation is because of down-regulation of MTP1.

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Authors: Yang, F., Liu, X.-B., Quinones, M., Melby, P. C., Ghio, A., & Haile, D. J.
Affiliations: Audie L. Murphy Memorial VA Hospital (US)
The University of Texas at San Antonio Health Science Center (US)
Environmental Protection Agency (US)
Corresponding author: Haile, David J.
ORCID: Melby, Peter C.
Ghio, Andrew
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2002-10
Volume: 277
Issue: 42
Pages: 39786-39791
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m201485200
OpenAlex: W2044318447
Cited by: 197
References: 44
Citations by year: 2026: 1 · 2025: 4 · 2024: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 14
FWCI: 7.87
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6590 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01dk053079-02)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK-53079)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: reticuloendothelial system, iron transport, inflammation, anemia of chronic disease, iron sequestration, lipopolysaccharide, TLR4, TNF-α, Leishmania donovani, spleen, liver, bone marrow, iron recycling
MeSH terms: Ferroportin, Animals, Immunohistochemistry, Inflammation, Iron, Kinetics, Lipopolysaccharides, Liver, Male, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Microscopy, Fluorescence, Oocytes, Protein Binding, Receptors, Cell Surface, RNA, Messenger, Spleen, Time Factors, Transfection, Tumor Necrosis Factor-alpha, Blotting, Western, Signal Transduction, Down-Regulation, Reverse Transcriptase Polymerase Chain Reaction, Cation Transport Proteins, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice

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Regulation of Reticuloendothelial Iron Transporter MTP1 (Slc11a3) by Inflammation

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