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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2008-6-2
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pubmed:abstractText |
Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in bronchial epithelial cell lines. Treatment of these cells with IL-1beta and TNF-alpha resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-kappaB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-kappaB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in Elf3 (homologous to human ESE-1) knockout mice, the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EHF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ELF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Elf3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1748-7838
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pubmed:author |
pubmed-author:CaoHuibiH,
pubmed-author:DuanRongqiR,
pubmed-author:FieldDeborahD,
pubmed-author:HertzogPaulP,
pubmed-author:KoehlerDavid RDR,
pubmed-author:NewnhamCatherine MCM,
pubmed-author:PostMartinM,
pubmed-author:PritchardMelanie AMA,
pubmed-author:TanswellA KeithAK,
pubmed-author:VOL NLN,
pubmed-author:WuJingJ,
pubmed-author:ZamelNoeN
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
649-63
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pubmed:dateRevised |
2010-5-11
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pubmed:meshHeading |
pubmed-meshheading:18475289-Animals,
pubmed-meshheading:18475289-Base Sequence,
pubmed-meshheading:18475289-Cell Line,
pubmed-meshheading:18475289-Cytokines,
pubmed-meshheading:18475289-DNA-Binding Proteins,
pubmed-meshheading:18475289-Down-Regulation,
pubmed-meshheading:18475289-Epithelial Cells,
pubmed-meshheading:18475289-Epithelium,
pubmed-meshheading:18475289-Humans,
pubmed-meshheading:18475289-Inflammation,
pubmed-meshheading:18475289-Inflammation Mediators,
pubmed-meshheading:18475289-Lipopolysaccharides,
pubmed-meshheading:18475289-Mice,
pubmed-meshheading:18475289-Mice, Knockout,
pubmed-meshheading:18475289-Molecular Sequence Data,
pubmed-meshheading:18475289-NF-kappa B,
pubmed-meshheading:18475289-Organ Specificity,
pubmed-meshheading:18475289-Promoter Regions, Genetic,
pubmed-meshheading:18475289-Protein Binding,
pubmed-meshheading:18475289-Proto-Oncogene Proteins,
pubmed-meshheading:18475289-Respiratory System,
pubmed-meshheading:18475289-Sequence Deletion,
pubmed-meshheading:18475289-Transcription Factors,
pubmed-meshheading:18475289-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation.
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pubmed:affiliation |
Department of Physiology and Experimental Medicine and Canadian Institutes of Health Research Group in Lung Development, The Hospital for Sick Children, The University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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