Source:http://linkedlifedata.com/resource/pubmed/id/16162660
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2006-1-11
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| pubmed:abstractText |
NADPH oxidase 1 (Nox1), a homolog of gp91(phox), is dominantly expressed in large intestinal epithelium, and reactive oxygen species derived from Nox1 are suggested to serve a role in host defense. We report that interferon (IFN)-gamma, a crucial transactivator of the gp91(phox) gene, also stimulates expression of Nox1 mRNA and protein in large intestinal epithelium (T84 cells), leading to fourfold upregulation of superoxide anion (O(2)(-)) generation. Introduction of small interfering Nox1 RNA completely blocked this priming. We cloned the region from -4,831 to +195 bp of the human Nox1 gene. To reveal IFN-gamma-responsive cis elements, we performed transient expression assays using a reporter gene driven by serially truncated Nox1 promoters in T84 cells. IFN-gamma-responsive elements were located between -4.3 and -2.6 kb, and one gamma-activated sequence (GAS) element present at -3,818 to -3,810 bp exhibited this IFN-gamma-dependent promoter activity. IFN-gamma caused tyrosine phosphorylation of signal transducer and activator of transcription 1 (STAT1) and produced a protein-GAS complex that was recognized by anti-STAT1 antibody. The introduction of three-point mutation of GAS, which did not interact with STAT1, completely canceled the IFN-gamma-dependent promoter activity of the region from -4,831 to +195 bp. A Janus protein tyrosine kinase 2 inhibitor (AG490) blocked the IFN-gamma-stimulated tyrosine phosphorylation of STAT1, promoter activity of the -4,831 to +195 bp region, Nox1 mRNA expression, and O(2)(-) production, also suggesting a crucial role of STAT1 and GAS in the IFN-gamma-stimulated transcription of the Nox1 gene. Our results support a potential contribution of Nox1 to mucosal host defense and inflammation in the colon.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/NOX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0363-6143
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
290
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
C433-43
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16162660-Amino Acid Sequence,
pubmed-meshheading:16162660-Base Sequence,
pubmed-meshheading:16162660-Cell Line,
pubmed-meshheading:16162660-Epithelial Cells,
pubmed-meshheading:16162660-Gene Expression Regulation,
pubmed-meshheading:16162660-Genes, Reporter,
pubmed-meshheading:16162660-Humans,
pubmed-meshheading:16162660-Inflammation,
pubmed-meshheading:16162660-Interferon-gamma,
pubmed-meshheading:16162660-Intestinal Mucosa,
pubmed-meshheading:16162660-Intestine, Large,
pubmed-meshheading:16162660-Molecular Sequence Data,
pubmed-meshheading:16162660-NADPH Oxidase,
pubmed-meshheading:16162660-Promoter Regions, Genetic,
pubmed-meshheading:16162660-STAT1 Transcription Factor,
pubmed-meshheading:16162660-Superoxides,
pubmed-meshheading:16162660-Transcription, Genetic,
pubmed-meshheading:16162660-Up-Regulation
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| pubmed:year |
2006
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| pubmed:articleTitle |
Interferon-gamma activates transcription of NADPH oxidase 1 gene and upregulates production of superoxide anion by human large intestinal epithelial cells.
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| pubmed:affiliation |
Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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