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Regulation of Reticuloendothelial Iron Transporter MTP1 (Slc11a3) by Inflammation
Open accessAbstract
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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“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
In the citing paper
“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
In the citing paper
“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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Metadata
- 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.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 277
- Issue
- 42
- Pages
- 39786-39791
- ISSN
- 0021-9258 (ISSN-L)
- 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
- 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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