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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021747,
umls-concept:C0040649,
umls-concept:C0185117,
umls-concept:C0220905,
umls-concept:C0442805,
umls-concept:C1415900,
umls-concept:C1420088,
umls-concept:C1521761,
umls-concept:C1533698,
umls-concept:C1948023,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2003-8-6
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pubmed:abstractText |
Natural-resistance associated macrophage protein 1 (Nramp1) encodes a transmembrane phagolysosomal protein exerting resistance toward infections with intracellular pathogens by a mechanism not fully elucidated so far. We used the murine macrophage cell line RAW264.7, stably transfected with functional (RAW-37) or nonfunctional (RAW-21) Nramp1, to study for differences in the expression of NO, a central antimicrobial effector molecule of macrophages. Following stimulation with IFN-gamma and LPS, Nramp1-expressing cells exhibit higher enzymatic activity of inducible NO synthase (iNOS) and increased cytoplasmic iNOS mRNA levels than RAW-21 cells. Time-course experiments showed that iNOS-mRNA levels remain increased in RAW-37 cells after prolonged cytokine stimulation while they decrease in RAW-21 cells. Reporter gene assays with iNOS-promoter luciferase constructs demonstrated an increased and prolonged promoter activity in Nramp1-resistant vs susceptible cells. This was paralleled by increased IFN regulatory factor 1 (IRF-1) expression and binding affinity to the iNOS promoter in RAW-37 cells, which may be related to enhanced STAT-1 binding affinity in these cells. A point mutation within the IRF-1 binding site of the iNOS promoter abolished the differences in iNOS transcription between RAW-21 and RAW-37 cells. Cells carrying functional Nramp1 express increased amounts of NO, which may be related to STAT-1-mediated stimulation of IRF-1 expression with subsequent prolonged activation of iNOS transcription. Enhanced NO expression may partly underlie the protection against infection with intracellular pathogens by Nramp1 functionality.
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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/Cation Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
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/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrites,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/natural resistance-associated...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
171
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1994-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12902503-Animals,
pubmed-meshheading:12902503-Blotting, Northern,
pubmed-meshheading:12902503-Cation Transport Proteins,
pubmed-meshheading:12902503-Cell Line,
pubmed-meshheading:12902503-DNA-Binding Proteins,
pubmed-meshheading:12902503-Down-Regulation,
pubmed-meshheading:12902503-Enzyme Activation,
pubmed-meshheading:12902503-Gene Expression Regulation,
pubmed-meshheading:12902503-Immunity, Innate,
pubmed-meshheading:12902503-Interferon Regulatory Factor-1,
pubmed-meshheading:12902503-Interferon-gamma,
pubmed-meshheading:12902503-Iron,
pubmed-meshheading:12902503-Lipopolysaccharides,
pubmed-meshheading:12902503-Macrophages,
pubmed-meshheading:12902503-Mice,
pubmed-meshheading:12902503-Mice, Inbred BALB C,
pubmed-meshheading:12902503-Nitric Oxide Synthase,
pubmed-meshheading:12902503-Nitric Oxide Synthase Type II,
pubmed-meshheading:12902503-Nitrites,
pubmed-meshheading:12902503-Phosphoproteins,
pubmed-meshheading:12902503-RNA, Messenger,
pubmed-meshheading:12902503-Salmonella typhimurium,
pubmed-meshheading:12902503-Transcription, Genetic,
pubmed-meshheading:12902503-Transfection,
pubmed-meshheading:12902503-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression.
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pubmed:affiliation |
Department of Internal Medicine, University Hospital of Innsbruck, Innsbruck, Austria.
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pubmed:publicationType |
Journal Article
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