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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
18
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pubmed:dateCreated |
1994-6-9
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pubmed:abstractText |
A glucocorticoid, dexamethasone, inhibited the production of a leukocyte chemotactic cytokine, interleukin 8 (IL-8), as well as mRNA expression by a glioblastoma cell line, T98G, stimulated with interleukin 1 (IL-1). Dexamethasone also inhibited IL-8 promoter-driven chloramphenicol acetyltransferase (CAT) activities induced by IL-1, suggesting that dexamethasone inhibited IL-8 production mainly at the transcriptional level. Moreover, CAT assay revealed that the nuclear factor-kappa B (NF-kappa B) binding site was the crucial cis-element required for conferring IL-1 responsiveness in conjunction with the CCAAT enhancer binding protein/nuclear factor-IL-6 (NF-IL6) and/or the AP-1 binding site(s). Mutation of either the AP-1 or NF-IL6 binding site did not abolish IL-8 gene repression by dexamethasone, suggesting that these sites were not targets for dexamethasone. Trimerized kappa B sequence in the IL-8 gene was enough for conferring the induction by IL-1 and inhibition by dexamethasone of CAT activity. Finally, dexamethasone diminished the IL-1-induced formation of NF-kappa B complexes, which were identified immunochemically to consist of p50 and p65, without reducing the amount of translocated factors. Collectively, dexamethasone interfered with the binding of the most essential transcription factor, NF-kappa B, to its cognate cis-element, thereby suppressing the transcription of IL-8 gene.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13289-95
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8175759-Amino Acid Sequence,
pubmed-meshheading:8175759-Base Sequence,
pubmed-meshheading:8175759-Biological Transport,
pubmed-meshheading:8175759-Cell Nucleus,
pubmed-meshheading:8175759-Dexamethasone,
pubmed-meshheading:8175759-Gene Expression Regulation,
pubmed-meshheading:8175759-Glioblastoma,
pubmed-meshheading:8175759-Humans,
pubmed-meshheading:8175759-Interleukin-1,
pubmed-meshheading:8175759-Interleukin-8,
pubmed-meshheading:8175759-Molecular Sequence Data,
pubmed-meshheading:8175759-NF-kappa B,
pubmed-meshheading:8175759-Transcription, Genetic,
pubmed-meshheading:8175759-Tumor Cells, Cultured
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pubmed:year |
1994
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pubmed:articleTitle |
Novel mechanism of glucocorticoid-mediated gene repression. Nuclear factor-kappa B is target for glucocorticoid-mediated interleukin 8 gene repression.
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pubmed:affiliation |
Department of Pharmacology, Kanazawa University, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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