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rdf:type |
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lifeskim:mentions |
umls-concept:C0002871,
umls-concept:C0014792,
umls-concept:C0014819,
umls-concept:C0021469,
umls-concept:C0026809,
umls-concept:C0033268,
umls-concept:C0205191,
umls-concept:C0205263,
umls-concept:C0376558,
umls-concept:C0392756,
umls-concept:C0919490,
umls-concept:C1522496,
umls-concept:C1706474,
umls-concept:C1711300,
umls-concept:C2700613
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pubmed:issue |
9
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pubmed:dateCreated |
2011-9-2
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pubmed:abstractText |
Anemia of chronic disease is a complication accompanying many inflammatory diseases. The proinflammatory cytokine IFN-? has been implicated in this form of anemia, but the underlying mechanism remains unclear. Here we describe a novel mouse model for anemia of chronic disease, in which enhanced CD27-mediated costimulation strongly increases the formation of IFN-?-producing effector T cells, leading to a progressive anemia. We demonstrate that the anemia in these mice is fully dependent on IFN-? and that this cytokine reduces both the life span and the formation of red blood cells. Molecular analysis revealed that IFN-? induces expression of the transcription factors of interferon regulatory factor-1 (IRF-1) and PU.1 in both murine and human erythroid precursors. We found that, on IFN-? stimulation, IRF-1 binds to the promoter of SPI.1 (PU.1) and induces PU.1 expression, leading to inhibition of erythropoiesis. Notably, down-regulation of either IRF-1 or PU.1 expression is sufficient to overcome IFN-?-induced inhibition of erythropoiesis. These findings reveal a molecular mechanism by which chronic exposure to IFN-? induces anemia.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD70,
http://linkedlifedata.com/resource/pubmed/chemical/CD70 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Irf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2578-88
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pubmed:meshHeading |
pubmed-meshheading:21725055-Anemia,
pubmed-meshheading:21725055-Animals,
pubmed-meshheading:21725055-Antigens, CD70,
pubmed-meshheading:21725055-Chronic Disease,
pubmed-meshheading:21725055-Colony-Forming Units Assay,
pubmed-meshheading:21725055-Disease Models, Animal,
pubmed-meshheading:21725055-Erythrocyte Aging,
pubmed-meshheading:21725055-Erythroid Precursor Cells,
pubmed-meshheading:21725055-Erythropoiesis,
pubmed-meshheading:21725055-Interferon Regulatory Factor-1,
pubmed-meshheading:21725055-Interferon-gamma,
pubmed-meshheading:21725055-Macrophages,
pubmed-meshheading:21725055-Mice,
pubmed-meshheading:21725055-Mice, Inbred C57BL,
pubmed-meshheading:21725055-Phagocytosis,
pubmed-meshheading:21725055-Proto-Oncogene Proteins,
pubmed-meshheading:21725055-RNA, Small Interfering,
pubmed-meshheading:21725055-Recombinant Fusion Proteins,
pubmed-meshheading:21725055-Specific Pathogen-Free Organisms,
pubmed-meshheading:21725055-Trans-Activators
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pubmed:year |
2011
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pubmed:articleTitle |
Chronic IFN-? production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis.
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pubmed:affiliation |
Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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