Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Open accessAbstract
Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor α (TNF-α), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation.
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Cytokines such as interleukin (IL)-1, IL-6, or IL-22 as well as bacterial LPS or endoplasmic reticulum stress induce the formation of hepcidin in the liver.
“Cytokines such as interleukin (IL)-1, IL-6, or IL-22 as well as bacterial LPS or endoplasmic reticulum stress induce the formation of the master regulator of iron homeostasis, hepcidin, in the liver (Nemeth et al., 2003; Vecchi et al., 2009; Armitage et al., 2011).”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nemeth et al., 2003
The Results and discussion section (page not supplied) reports strong hepcidin mRNA induction by IL-6 in human hepatocytes and a small increase with LPS alone. It reports IL-1 induction only after 24 hours, probably indirectly through IL-6; the copy does not address IL-22 or endoplasmic reticulum stress. Thus, this source supports some, but not all, of the factors listed in the jointly cited sentence. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPatients with anemia of inflammation due to inflammatory disorders or infections have markedly increased excretion of urinary hepcidin.
“patients with AI due to inflammatory disorders or infections had markedly increased excretion of urinary hepcidin”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
IL-6 strongly induces hepcidin mRNA in fresh human hepatocytes.
“strong induction of hepcidin mRNA by IL-6”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
IL-1α and TNFα do not strongly induce hepcidin mRNA in fresh human hepatocytes.
“but not IL-1 α or TNFα”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
Hepcidin production is diminished in the most common form of hemochromatosis caused by mutations in the HFE gene.
“in the most common form of hemochromatosis, that caused by mutations in the HFE gene”
From IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin (2004) · cites this paper as [12]
The Results and discussion (page unavailable) compare urinary hepcidin in patients with well-controlled hereditary hemochromatosis with levels in patients with anemia of inflammation, but do not say hepcidin production is diminished relative to healthy people. A search for HFE mutations found no passage identifying the hemochromatosis patients as having HFE-related disease. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Hepcidin levels are increased during infection and inflammation, and its release is upregulated in response to inflammatory cytokines, in particular interleukin-6.
“Hepcidin levels are increased during infection and inflammation. Its release is upregulated in response to inflammatory cytokines, in particular interleukin-6 (IL-6) [16–18].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [18]
Hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker.
“However, hepcidin is overexpressed in inflammatory disease and is an early inflammatory marker [245,341-345].”
Increased inflammatory activity with reduced intestinal absorption of Fe, stronger sequestration of Fe in macrophages, and lowered Fe in serum is reflected in increased serum ferritin levels.
“Increased inflammatory activity with reduced intestinal absorption of Fe, with stronger sequestration of Fe in macrophages and lowered Fe, are reflected in the serum, which, at the same time, shows an increase in serum ferritin levels [88,89,90].”
From Iron Deficiency in Obesity and after Bariatric Surgery (2021) · cites this paper as [90]
Hepcidin expression is induced by hyperferremia, cytokines such as IL-1, IL-6, and IL-22, and recognition of bacterial lipopolysaccharide by TLR4.
“Hepcidin expression is regulated mainly at the level of transcription of the hepcidin (HAMP) gene, being induced in response to: (i) hyperferremia, that is, higher than normal levels of circulating Fe, (ii) cytokines, for example, interleukin (IL)-1, IL-6, and IL-22, or (iii) recognition of bacterial lipopolysaccharide by Toll-like receptor 4 (TLR4) [59][60][61]”
From The Iron age of host–microbe interactions (2015) · cites this paper as [61]
In inflammation, IL-6 and Activin B induce hepcidin as an acute-phase protein through STAT3 and SMAD4 signaling.
“During inflammation, hepcidin is induced as an acute-phase reactant by IL-6 and Activin B via STAT3 and SMAD4, respectively (8,9).”
From Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia (2017) · cites this paper as [9]
HAMP transcription in hepatocytes is induced by iron, by microbial sensing through pattern recognition receptors, or by innate immune cytokines including IL-1β, IL-6, and IL-22.
“HAMP transcription is induced in hepatocytes in response to i) Fe, ii) microbial sensing by pattern recognition receptors (PRR) or iii) cytokines produced by innate immune cells, including IL-1β, IL-6 or IL-22 (19, 22–24).”
From Innate Nutritional Immunity (2018) · cites this paper as [24]
Hepcidin is an acute phase protein upregulated by inflammatory cytokines, notably IL-6.
“but is also an acute phase protein upregulated by inflammatory cytokines, notably IL-6 [18–20].”
From Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans (2015) · cites this paper as [20]
Hepcidin has been detected and quantitated in urine samples and, with more difficulty, in serum.
“It has been detected and quantitated in urine samples, 91,96 and, with more difficulty, in serum.97”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [96]
Induction of hepcidin expression in response to inflammation might explain the anemia of chronic disease.
“We found that the hepatocytelike cells of the adenomas expressed very high levels of hepcidin 100 and speculated that our results could be generalized-that induction of hepcidin expression in response to inflammation might explain the anemia of chronic disease.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [96]
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Cites
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734 · see citing works
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168 · see citing works
Self-citationPigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697 · see citing works
LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324 · see citing works
Nicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X., Devaux, I., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215686 · Cited by 1,214 · see citing works
Regulation of ferritin genes and protein
Torti, F. M., & Torti, S. V. (2002) · Blood · doi:10.1182/blood.v99.10.3505 · Cited by 1,173 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Fleming RE, Sly WS. Hepcidin: a putative iron- regulatory hormone relevant to hereditary hemo- chromatosis and the anemia of chronic disease. Proc Natl Acad Sci U S A. 2001;98:8160-8162.
- Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci U S A. 2001; 98:8780-8785.
- Nicolas G, Bennoun M, Porteu A, et al. Severe iron deficiency anemia in transgenic mice ex- pressing liver hepcidin. Proc Natl Acad Sci U S A. 2002;99:4596-4601.
- Shike H, Lauth X, Westerman ME, et al. Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge. Eur J Biochem. 2002;269: 2232-2237.
- Hunter HN, Fulton DB, Ganz T, Vogel HJ. The solution structure of human hepcidin, a peptide- hormone with antimicrobial activity that is in- volved in iron uptake and hereditary hemochro- matosis. J Biol Chem. 2002;277:37597-37603.
- Moshage H. Cytokines and the hepatic acute phase response. J Pathol. 1997;181:257-266.
Cited by
Sorted by citations
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 · see citing works
Self-citationNemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650 · see citing works
Self-citationHepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544 · see citing works
Self-citationZimmermann, M. B., & Hurrell, R. F. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61235-5 · Cited by 1,405 · see citing works
Iron bioavailability and dietary reference values
Hurrell, R., & Egli, I. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.28674f · Cited by 1,359 · see citing works
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122 · see citing works
Self-citationEmery, P., Keystone, E., Tony, H. P., Cantagrel, A., van Vollenhoven, R., Sanchez, A., Alecock, E., Lee, J., & Kremer, J. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.092932 · Cited by 1,104 · see citing works
Essential metals in health and disease
Jomova, K., Makova, M., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., Rhodes, C. J., & Valko, M. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110173 · Cited by 1,121 · see citing works
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 · see citing works
Hereditary Hemochromatosis — A New Look at an Old Disease
Pietrangelo, A. (2004) · New England Journal of Medicine · doi:10.1056/nejmra031573 · Cited by 992 · see citing works
Interleukin-6 induces hepcidin expression through STAT3
Wrighting, D. M., & Andrews, N. C. (2006) · Blood · doi:10.1182/blood-2006-06-027631 · Cited by 983 · see citing works
Mutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L. E., Franchini, P. L., Dubé, M.-P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1274 · Cited by 974 · see citing works
Self-citationHepcidin and iron regulation, 10 years later
Ganz, T. (2011) · Blood · doi:10.1182/blood-2011-01-258467 · Cited by 962 · see citing works
Self-citationBMP6 is a key endogenous regulator of hepcidin expression and iron metabolism
Andriopoulos Jr, B., Corradini, E., Xia, Y., Faasse, S. A., Chen, S., Grgurevic, L., Knutson, M. D., Pietrangelo, A., Vukicevic, S., Lin, H. Y., et al. (2009) · Nature Genetics · doi:10.1038/ng.335 · Cited by 769 · see citing works
Regulation of Iron Metabolism by Hepcidin
Nemeth, E., & Ganz, T. (2006) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.26.061505.111303 · Cited by 756 · see citing works
Self-citationForging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623 · see citing works
A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression
Wang, R.-H., Li, C., Xu, X., Zheng, Y., Xiao, C., Zerfas, P., Cooperman, S., Eckhaus, M., Rouault, T., Mishra, L., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.010 · Cited by 614 · see citing works
The serine protease TMPRSS6 is required to sense iron deficiency
Du, X., She, E., Gelbart, T., Truksa, J., Lee, P., Xia, Y., Khovananth, K., Mudd, S., Mann, N., Moresco, E. M. Y., et al. (2008) · Science · doi:10.1126/science.1157121 · Cited by 578 · see citing works
STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation
Verga Falzacappa, M. V., Vujic Spasic, M., Kessler, R., Stolte, J., Hentze, M. W., & Muckenthaler, M. U. (2007) · Blood · doi:10.1182/blood-2006-07-033969 · Cited by 567 · see citing works
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554 · see citing works
Zimmermann, M. B., Chassard, C., Rohner, F., N'Goran, E. K., Nindjin, C., Dostal, A., Utzinger, J., Ghattas, H., Lacroix, C., & Hurrell, R. F. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.004564 · Cited by 520 · see citing works
Bekri, S., Gual, P., Anty, R., Luciani, N., Dahman, M., Ramesh, B., Iannelli, A., Staccini–Myx, A., Casanova, D., Ben Amor, I., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.07.007 · Cited by 496 · see citing works
Viral infection and iron metabolism
Drakesmith, H., & Prentice, A. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1930 · Cited by 469 · see citing works
Knutson, M. D., Oukka, M., Koss, L. M., Aydemir, F., & Wessling-Resnick, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409409102 · Cited by 479 · see citing works
Suppression of hepcidin during anemia requires erythropoietic activity
Pak, M., Lopez, M. A., Gabayan, V., Ganz, T., & Rivera, S. (2006) · Blood · doi:10.1182/blood-2006-06-028787 · Cited by 472 · see citing works
Self-citationHepcidin in iron overload disorders
Papanikolaou, G., Tzilianos, M., Christakis, J. I., Bogdanos, D., Tsimirika, K., MacFarlane, J., Goldberg, Y. P., Sakellaropoulos, N., Ganz, T., & Nemeth, E. (2005) · Blood · doi:10.1182/blood-2004-12-4844 · Cited by 445 · see citing works
Self-citationBrissot, P., Pietrangelo, A., Adams, P. C., de Graaff, B., McLaren, C. E., & Loréal, O. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.16 · Cited by 430 · see citing works
Macrophages and Iron Metabolism
Soares, M. P., & Hamza, I. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.016 · Cited by 401 · see citing works
Hepcidin—a regulator of intestinal iron absorption and iron recycling by macrophages
GANZ, T. (2005) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2004.08.020 · Cited by 393 · see citing works
Self-citationIron Sequestration and Anemia of Inflammation
Ganz, T., & Nemeth, E. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.06.001 · Cited by 361 · see citing works
Self-citationMolecular control of iron transport
Ganz, T. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006070802 · Cited by 353 · see citing works
Suppression of iron-regulatory hepcidin by vitamin D
Bacchetta, J., Zaritsky, J. J., Sea, J. L., Chun, R. F., Lisse, T. S., Zavala, K., Nayak, A., Wesseling-Perry, K., Westerman, M., Hollis, B. W., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013040355 · Cited by 350 · see citing works
Iron imports. IV. Hepcidin and regulation of body iron metabolism
Ganz, T., & Nemeth, E. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00412.2005 · Cited by 347 · see citing works
Self-citationInflammation and iron deficiency in the hypoferremia of obesity
Yanoff, L. B., Menzie, C. M., Denkinger, B., Sebring, N. G., McHugh, T., Remaley, A. T., & Yanovski, J. A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803625 · Cited by 341 · see citing works
Iron at the interface of immunity and infection
Nairz, M., Haschka, D., Demetz, E., & Weiss, G. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00152 · Cited by 325 · see citing works
“Cytokines such as interleukin (IL)-1, IL-6, or IL-22 as well as bacterial LPS or endoplasmic reticulum stress induce the formation of the master regulator of iron homeostasis, hepcidin, in the liver (Nemeth et al., 2003; Vecchi et al., 2009; Armitage et al., 2011).”
BackgroundIron metabolism in the anemia of chronic disease
Weiss, G. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.006 · Cited by 322 · see citing works
ER Stress Controls Iron Metabolism Through Induction of Hepcidin
Vecchi, C., Montosi, G., Zhang, K., Lamberti, I., Duncan, S. A., Kaufman, R. J., & Pietrangelo, A. (2009) · Science · doi:10.1126/science.1176639 · Cited by 310 · see citing works
STAT3 Is Required for IL-6-gp130–Dependent Activation of Hepcidin In Vivo
Pietrangelo, A., Dierssen, U., Valli, L., Garuti, C., Rump, A., Corradini, E., Ernst, M., Klein, C., & Trautwein, C. (2007) · Gastroenterology · doi:10.1053/j.gastro.2006.10.018 · Cited by 315 · see citing works
Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis
Nicolas, G., Viatte, L., Lou, D.-Q., Bennoun, M., Beaumont, C., Kahn, A., Andrews, N. C., & Vaulont, S. (2003) · Nature Genetics · doi:10.1038/ng1150 · Cited by 311 · see citing works
Rivera, S., Nemeth, E., Gabayan, V., Lopez, M. A., Farshidi, D., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2005-04-1766 · Cited by 308 · see citing works
Self-citationAn overview of molecular basis of iron metabolism regulation and the associated pathologies
Silva, B., & Faustino, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.011 · Cited by 300 · see citing works
Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones
Peeling, P., Dawson, B., Goodman, C., Landers, G., & Trinder, D. (2008) · European Journal of Applied Physiology · doi:10.1007/s00421-008-0726-6 · Cited by 292 · see citing works
Autocrine formation of hepcidin induces iron retention in human monocytes
Theurl, I., Theurl, M., Seifert, M., Mair, S., Nairz, M., Rumpold, H., Zoller, H., Bellmann-Weiler, R., Niederegger, H., Talasz, H., et al. (2008) · Blood · doi:10.1182/blood-2007-05-090019 · Cited by 275 · see citing works
Iron-withholding strategy in innate immunity
Ong, S. T., Shan Ho, J. Z., Ho, B., & Ding, J. L. (2006) · Immunobiology · doi:10.1016/j.imbio.2006.02.004 · Cited by 269 · see citing works
Lin, L., Valore, E. V., Nemeth, E., Goodnough, J. B., Gabayan, V., & Ganz, T. (2007) · Blood · doi:10.1182/blood-2007-04-087593 · Cited by 267 · see citing works
Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis
Lesbordes-Brion, J.-C., Viatte, L., Bennoun, M., Lou, D.-Q., Ramey, G., Houbron, C., Hamard, G., Kahn, A., & Vaulont, S. (2006) · Blood · doi:10.1182/blood-2006-02-003376 · Cited by 257 · see citing works
Sequestration and scavenging of iron in infection
Parrow, N. L., Fleming, R. E., & Minnick, M. F. (2013) · Infection and Immunity · doi:10.1128/iai.00602-13 · Cited by 261 · see citing works
Kulaksiz, H., Theilig, F., Bachmann, S., Gehrke, S. G., Rost, D., Janetzko, A., Cetin, Y., & Stremmel, W. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.05729 · Cited by 241 · see citing works
Sasu, B. J., Cooke, K. S., Arvedson, T. L., Plewa, C., Ellison, A. R., Sheng, J., Winters, A., Juan, T., Li, H., Begley, C. G., et al. (2010) · Blood · doi:10.1182/blood-2009-09-245977 · Cited by 251 · see citing works
Proinflammatory state, hepcidin, and anemia in older persons
Ferrucci, L., Semba, R. D., Guralnik, J. M., Ershler, W. B., Bandinelli, S., Patel, K. V., Sun, K., Woodman, R. C., Andrews, N. C., Cotter, R. J., et al. (2010) · Blood · doi:10.1182/blood-2009-02-201087 · Cited by 245 · see citing works
Self-citationOxidative Stress and the Homeodynamics of Iron Metabolism
Bresgen, N., & Eckl, P. (2015) · Biomolecules · doi:10.3390/biom5020808 · Cited by 247 · see citing works
Host-mediated regulation of superinfection in malaria
Portugal, S., Carret, C., Recker, M., Armitage, A. E., Gonçalves, L. A., Epiphanio, S., Sullivan, D., Roy, C., Newbold, C. I., Drakesmith, H., et al. (2011) · Nature Medicine · doi:10.1038/nm.2368 · Cited by 232 · see citing works
Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases
Bissinger, R., Bhuyan, A. A. M., Qadri, S. M., & Lang, F. (2019) · The FEBS Journal · doi:10.1111/febs.14606 · Cited by 239 · see citing works
Valore, E. V., & Ganz, T. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2007.07.009 · Cited by 234 · see citing works
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis
Sow, F. B., Florence, W. C., Satoskar, A. R., Schlesinger, L. S., Zwilling, B. S., & Lafuse, W. P. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0407216 · Cited by 229 · see citing works
The Iron age of host–microbe interactions
Soares, M. P., & Weiss, G. (2015) · The EMBO Reports · doi:10.15252/embr.201540558 · Cited by 227 · see citing works
Brasse–Lagnel, C., Karim, Z., Letteron, P., Bekri, S., Bado, A., & Beaumont, C. (2011) · Gastroenterology · doi:10.1053/j.gastro.2010.12.037 · Cited by 230 · see citing works
Song, S.-N. J., Tomosugi, N., Kawabata, H., Ishikawa, T., Nishikawa, T., & Yoshizaki, K. (2010) · Blood · doi:10.1182/blood-2010-03-271791 · Cited by 228 · see citing works
Zimmermann, M. B., Zeder, C., Muthayya, S., Winichagoon, P., Chaouki, N., Aeberli, I., & Hurrell, R. F. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.43 · Cited by 225 · see citing works
The hematologic consequences of obesity
Purdy, J. C., & Shatzel, J. J. (2021) · European Journal Of Haematology · doi:10.1111/ejh.13560 · Cited by 227 · see citing works
Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis
Gao, H., Jin, Z., Bandyopadhyay, G., Wang, G., Zhang, D., Rocha, K. C. E., Liu, X., Zhao, H., Kisseleva, T., Brenner, D. A., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.07.006 · Cited by 224 · see citing works
Hepcidin: regulation of the master iron regulator
Rishi, G., Wallace, D. F., & Subramaniam, V. N. (2015) · Bioscience Reports · doi:10.1042/bsr20150014 · Cited by 223 · see citing works
Lee, P., Peng, H., Gelbart, T., & Beutler, E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403108101 · Cited by 221 · see citing works
Hepcidin and Host Defense against Infectious Diseases
Michels, K., Nemeth, E., Ganz, T., & Mehrad, B. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1004998 · Cited by 205 · see citing works
Self-citationHepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia
Rivera, S., Liu, L., Nemeth, E., Gabayan, V., Sorensen, O. E., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2004-08-3375 · Cited by 196 · see citing works
Self-citationCorradini, E., Meynard, D., Wu, Q., Chen, S., Ventura, P., Pietrangelo, A., & Babitt, J. L. (2011) · Hepatology · doi:10.1002/hep.24359 · Cited by 194 · see citing works
Ashby, D. R., Gale, D. P., Busbridge, M., Murphy, K. G., Duncan, N. D., Cairns, T. D., Taube, D. H., Bloom, S. R., Tam, F. W. K., Chapman, R., et al. (2010) · Haematologica · doi:10.3324/haematol.2009.013136 · Cited by 191 · see citing works
Besson-Fournier, C., Latour, C., Kautz, L., Bertrand, J., Ganz, T., Roth, M.-P., & Coppin, H. (2012) · Blood · doi:10.1182/blood-2012-02-411470 · Cited by 179 · see citing works
Self-citationNairz, M., Theurl, I., Ludwiczek, S., Theurl, M., Mair, S. M., Fritsche, G., & Weiss, G. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.00942.x · Cited by 182 · see citing works
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Merle, U., Fein, E., Gehrke, S. G., Stremmel, W., & Kulaksiz, H. (2007) · Endocrinology · doi:10.1210/en.2006-1331 · Cited by 173 · see citing works
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Self-citationGardenghi, S., Renaud, T. M., Meloni, A., Casu, C., Crielaard, B. J., Bystrom, L. M., Greenberg-Kushnir, N., Sasu, B. J., Cooke, K. S., & Rivella, S. (2014) · Blood · doi:10.1182/blood-2013-08-521625 · Cited by 107 · see citing works
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Xu, J., Jia, Z., Knutson, M. D., & Leeuwenburgh, C. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13022368 · Cited by 103 · see citing works
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Michels, K. R., Zhang, Z., Bettina, A. M., Cagnina, R. E., Stefanova, D., Burdick, M. D., Vaulont, S., Nemeth, E., Ganz, T., & Mehrad, B. (2017) · JCI Insight · doi:10.1172/jci.insight.92002 · Cited by 93 · see citing works
Self-citationVolke, M., Gale, D. P., Maegdefrau, U., Schley, G., Klanke, B., Bosserhoff, A.-K., Maxwell, P. H., Eckardt, K.-U., & Warnecke, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007875 · Cited by 93 · see citing works
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Nairz, M., Schroll, A., Demetz, E., Tancevski, I., Theurl, I., & Weiss, G. (2015) · Immunobiology · doi:10.1016/j.imbio.2014.09.010 · Cited by 89 · see citing works
Ruivard, M., Lainé, F., Ganz, T., Olbina, G., Westerman, M., Nemeth, E., Rambeau, M., Mazur, A., Gerbaud, L., Tournilhac, V., et al. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.01.029 · Cited by 89 · see citing works
Self-citationConditional deletion of ferritin H in mice induces loss of iron storage and liver damage #
Darshan, D., Vanoaica, L., Richman, L., Beermann, F., & Kühn, L. C. (2009) · Hepatology · doi:10.1002/hep.23058 · Cited by 86 · see citing works
The impact of metal availability on immune function during infection
Monteith, A. J., & Skaar, E. P. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.08.004 · Cited by 83 · see citing works
Sanad, M., Osman, M., & Gharib, A. (2011) · Italian Journal of Pediatrics · doi:10.1186/1824-7288-37-34 · Cited by 85 · see citing works
A variant erythroferrone disrupts iron homeostasis in <i>SF3B1</i> -mutated myelodysplastic syndrome
Bondu, S., Alary, A.-S., Lefèvre, C., Houy, A., Jung, G., Lefebvre, T., Rombaut, D., Boussaid, I., Bousta, A., Guillonneau, F., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5467 · Cited by 85 · see citing works
Self-citation
- Authors
- Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-04-01
- Volume
- 101
- Issue
- 7
- Pages
- 2461-2463
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2059080581
- Cited by
- 1,417
- References
- 6
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 27 · 2023: 44 · 2022: 41 · 2021: 61 · 2020: 54 · 2019: 56 · 2018: 45 · 2017: 56 · 2016: 51 · 2015: 66 · 2014: 85 · 2013: 82 · 2012: 68
- FWCI
- 35.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, anemia of chronic disease, acute phase proteins, iron overload, iron absorption, iron recycling, serum ferritin, interleukin-6, hepatocytes, inflammation, iron stores
- MeSH terms
- Acute-Phase Proteins, Anemia, Ferritins, Humans, Infections, Inflammation, Interleukin-1, Iron, RNA, Messenger, Tumor Necrosis Factor-alpha, Interleukin-6, Case-Control Studies, Iron Overload, Hepatocytes, Antimicrobial Cationic Peptides, Hepcidins
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