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

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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  • FPN1 levels are also reduced by transcriptional downregulation, which limits macrophage iron export and fosters iron storage in the cytoplasm.

    “In parallel, FPN1 levels are also reduced by transcriptional downregulation, which limits macrophage iron export and fosters iron storage in the cytoplasm (Ludwiczek et al., 2003;Yang et al., 2002).”

    From Iron in infection and immunity (2020) · cites this paper as Yang et al., 2002

  • Macrophage iron content is further expanded via an inhibitory effect of IFN-γ and LPS on ferroportin transcription, reducing cellular iron egress.

    “Macrophage iron content is further expanded via an inhibitory effect of IFN-γ and LPS on ferroportin transcription thereby reducing cellular iron egress (Yang et al., 2002; Ludwiczek et al., 2003).”

    From Iron at the interface of immunity and infection (2014) · cites this paper as Yang et al., 2002

  • Yeast Mrs3 and Mrs4 serve as mitochondrial iron-transport proteins and cooperate with YFH1 in providing iron for heme synthesis.

    “Yeast Mrs3 and Mrs4 were shown to serve as mitochondrial iron-transport proteins (94) and to cooperate with YFH1 in providing iron for heme synthesis (335).”

    From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [335]

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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
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
Licence
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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