The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice
Open accessAbstract
Mice deficient in the hemochromatosis gene, Hfe, have attenuated inflammatory responses to Salmonella infection associated with decreased macrophage TNF-alpha and IL-6 biosynthesis after exposure to LPS. In this study, we show that the abnormal cytokine production is related to impaired TLR4 signaling. Despite their abnormal response to LPS, Hfe KO macrophages produced amounts of TNF-alpha similar to those in WT cells after TLR2 stimulation. Consistent with this finding, LPS-induced activation of Mal/MyD88-dependent events was normal in the mutant macrophages. However, LPS-induced IFN-beta expression, a TRAM/TRIF-dependent response activated by TLR4, was reduced by Hfe deficiency. This reduction could be replicated in WT macrophages with the use of iron chelators. In contrast, TLR3-activated expression of IFN-beta, a TRIF-dependent response, was normal in Hfe KO macrophages and was unaffected by iron chelation. Our data suggest that low intracellular iron selectively impairs signaling via the TLR4/TRAM/TRIF pathway proximal to TRIF and results in reduced LPS-induced cytokine expression. Furthermore, by mimicking the altered iron metabolism associated with Hfe deficiency, we found that 3 different inhibitors of hepcidin attenuated Salmonella-induced and noninfectious enterocolitis. Thus, manipulation of iron homeostasis could represent a new therapeutic approach to controlling inflammation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Hepcidin deficiency results in altered tissue iron distribution and iron-depleted macrophages, and this could potentially affect innate immune signaling (Oexle et al., 2003; Wang et al., 2009).”
From Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus (2015) · cites this paper as Wang et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664
Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., et al. (2003) · Science · doi:10.1126/science.1087262 · Cited by 3,286
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
Kagan, J. C., Su, T., Horng, T., Chow, A. Y., Akira, S., & Medzhitov, R. M. (2008) · Nature Immunology · doi:10.1038/ni1569 · Cited by 1,310
Self-citationDorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
Yu, P. B., Hong, C. C., Sachidanandan, C., Babitt, J. L., Deng, D. Y., Hoyng, S. A., Lin, H. Y.-F., Bloch, K. D., & Peterson, R. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.54 · Cited by 1,059
Self-citationYamamoto, M., Sato, S., Hemmi, H., Uematsu, S., Hoshino, K., Kaisho, T., Takeuchi, O., Takeda, K., & Akira, S. (2003) · Nature Immunology · doi:10.1038/ni986 · Cited by 1,052
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression
Babitt, J. L., Huang, F. W., Wrighting, D. M., Xia, Y., Sidis, Y., Samad, T. A., Campagna, J. A., Chung, R. T., Schneyer, A. L., Woolf, C. J., et al. (2006) · Nature Genetics · doi:10.1038/ng1777 · Cited by 1,026
Self-citationBarthel, M., Hapfelmeier, S., Quintanilla-Martínez, L., Kremer, M., Rohde, M., Hogardt, M., Pfeffer, K., Rüssmann, H., & Hardt, W.-D. (2003) · Infection and Immunity · doi:10.1128/iai.71.5.2839-2858.2003 · Cited by 1,020
Toll‐like Receptor and RIG‐1‐like Receptor Signaling
Kawai, T., & Akira, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.020 · Cited by 1,014
Sazawal, S., Black, R. E., Ramsan, M., Chwaya, H. M., Stoltzfus, R. J., Dutta, A., Dhingra, U., Kabole, I., Deb, S., Othman, M. K., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)67962-2 · Cited by 981
Research works printed but not linked: 2
- Moyo, 1997, Cent. Afr. J. Med., 43, 334
- 10.1001/archinte.151.8.1606 · DOI · Paper page
Cited by
Sorted by citations
Hepcidin and the iron-infection axis
Drakesmith, H., & Prentice, A. M. (2012) · Science · doi:10.1126/science.1224577 · Cited by 686
Iron Homeostasis and the Inflammatory Response
Wessling-Resnick, M. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104804 · Cited by 480
Overview of iron metabolism in health and disease
Dev, S., & Babitt, J. L. (2017) · Hemodialysis International · doi:10.1111/hdi.12542 · Cited by 499
Self-citationDifferential regulation of iron homeostasis during human macrophage polarized activation
Recalcati, S., Locati, M., Marini, A., Santambrogio, P., Zaninotto, F., De Pizzol, M., Zammataro, L., Girelli, D., & Cairo, G. (2010) · European Journal of Immunology · doi:10.1002/eji.200939889 · Cited by 438
Cellular Metabolism and Macrophage Functional Polarization
Zhu, L., Zhao, Q., Yang, T., Ding, W., & Zhao, Y. X. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.969421 · Cited by 438
Metadata
- Authors
- Wang, L., Harrington, L., Trebicka, E., Shi, H. N., Kagan, J. C., Hong, C. C., Lin, H. Y., Babitt, J. L., & Cherayil, B. J.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Boston Children's Hospital (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Cherayil, Bobby J.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2009-10-05
- Volume
- 119
- Issue
- 11
- Pages
- 3322-8
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2769199
- OpenAlex
- W2167404536
- Cited by
- 162
- References
- 44
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 14 · 2018: 9 · 2017: 6 · 2016: 7 · 2015: 11 · 2014: 13 · 2013: 10 · 2012: 9
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (R01 071837)
- National Heart, Lung, and Blood Institute (K08HL081535)
- National Institute of Allergy and Infectious Diseases (R00AI072955)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK040561)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- TLR4 signaling, iron homeostasis, hemochromatosis, macrophages, lipopolysaccharide, interferon-beta, TLR2, TLR3, TNF-α, interleukin-6, salmonellosis, enterocolitis, inflammation, iron chelation
- MeSH terms
- Animals, Enterocolitis, Gene Expression Regulation, Hemochromatosis, Homeostasis, Immunity, Innate, Inflammation, Iron, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Salmonella Infections, Signal Transduction, Mice, Knockout, Toll-Like Receptor 4, Mice, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
