The DOI matches its Crossref record; 50 of the 52 references it cites were found in a registry or an index.
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis
Abstract
Hepcidin is an antimicrobial peptide produced by the liver in response to inflammatory stimuli and iron overload. Hepcidin regulates iron homeostasis by mediating the degradation of the iron export protein ferroportin 1, thereby inhibiting iron absorption from the small intestine and release of iron from macrophages. Here, we examined the expression of hepcidin in macrophages infected with the intracellular pathogens Mycobacterium avium and Mycobacterium tuberculosis. Stimulation of the mouse RAW264.7 macrophage cell line and mouse bone marrow-derived macrophages with mycobacteria and IFN-γ synergistically induced high levels of hepcidin mRNA and protein. Similar results were obtained using the human THP-1 monocytic cell line. Stimulation of macrophages with the inflammatory cytokines IL-6 and IL-β did not induce hepcidin mRNA expression. Iron loading inhibited hepcidin mRNA expression induced by IFN-γ and M. avium, and iron chelation increased hepcidin mRNA expression. Intracellular protein levels and secretion of hepcidin were determined by a competitive chemiluminescence ELISA. Stimulation of RAW264.7 cells with IFN-γ and M. tuberculosis induced intracellular expression and secretion of hepcidin. Furthermore, confocal microscopy analyses showed that hepcidin localized to the mycobacteria-containing phagosomes. As hepcidin has been shown to possess direct antimicrobial activity, we investigated its activity against M. tuberculosis. We found that hepcidin inhibited M. tuberculosis growth in vitro and caused structural damage to the mycobacteria. In summary, our data show for the first time that hepcidin localizes to the phagosome of infected, IFN-γ-activated cells and has antimycobacterial activity.
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“However, M. tuberculosis can also stimulate the formation of hepcidin in MΦs and subvert the stimulation of ferroportin-mediated iron excess and ensure iron retention within the MO (197).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [197]
In the citing paper
“Similarly, very high concentrations of hepcidin have been shown to inhibit M. tuberculosis growth in vitro [32], but it is unknown whether these concentrations are relevant to in vivo infections.”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“This effect has been demonstrated convincingly in vitro”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“hepcidin induces iron accumulation in macrophages”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“may be detrimental in defense against pathogens that occupy this intracellular niche”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“but is not supported by in vivo data [32,39–43,49–55]”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
In the citing paper
“Detrimental, by promoting sequestration of iron in macrophages”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [32]
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Metadata
- Authors
- Sow, F. B., Florence, W. C., Satoskar, A. R., Schlesinger, L. S., Zwilling, B. S., & Lafuse, W. P.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Lafuse, William P
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-03
- Volume
- 82
- Issue
- 4
- Pages
- 934-945
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2107072141
- Cited by
- 229
- References
- 52
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 6 · 2022: 12 · 2021: 19 · 2020: 7 · 2019: 12 · 2018: 9 · 2017: 14 · 2016: 10 · 2015: 17 · 2014: 12 · 2013: 18 · 2012: 13
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RO1DK-57667)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- hepcidin, macrophages, tuberculosis, Mycobacterium tuberculosis, Mycobacterium avium, iron homeostasis, ferroportin 1, interferon-gamma, antimicrobial activity, phagosome, host defense, iron chelation, iron loading
- MeSH terms
- Animals, Cell Line, Gene Expression Regulation, Homeostasis, Humans, Immunity, Innate, Interferon-gamma, Intestinal Absorption, Iron, Iron Chelating Agents, Liver, Mycobacterium avium, Mycobacterium tuberculosis, Phagosomes, RNA, Messenger, Tuberculosis, Iron Overload, Antimicrobial Cationic Peptides, Mice, Hepcidins
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