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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0024109,
umls-concept:C0035696,
umls-concept:C0079633,
umls-concept:C0079904,
umls-concept:C0085828,
umls-concept:C0205360,
umls-concept:C0221908,
umls-concept:C0441655,
umls-concept:C1519595,
umls-concept:C2349975
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pubmed:dateCreated |
1998-4-9
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pubmed:abstractText |
Inhibition of protein synthesis may result in superinduction of short-lived transcripts and has been attributed variably to stabilization of transcripts and/or increased gene transcription. Little is known about the kinetics of these processes and relevant transcriptional elements have not been identified. In this study, we describe superinduction of interleukin 8 (IL-8) mRNA, an important inflammatory mediator, in lung epithelial-like H292 cells and identify the underlying molecular mechanisms and their kinetics. Cycloheximide (CHI, 10 microg/ml), an inhibitor of protein synthesis, maximally increased IL-8 mRNA levels 30-fold in H292 cells. Tumour necrosis factor alpha (TNF-alpha), which induced IL-8 mRNA 3-fold, synergized with CHI causing a 150-fold increase at 6 h. CHI early on increased the stability of IL-8 mRNA (from 40 min in cells cultured with medium to more than 4 h with CHI). CHI also increased transcription as shown by transfection with IL-8 promoter constructs. Truncated and mutated constructs identified NF-kappaB and AP-1 binding sites as primary cis-acting elements in IL-8 gene transcription and IL-8 mRNA superinduction. Electrophoretic mobility shift assays indicated that CHI increased NF-kappaB and prolonged AP-1 DNA-binding activities and that the synergism of TNF-alpha and CHI on IL-8 mRNA expression was paralleled by a further increase of AP-1 DNA-binding activity. This synergism was still noticed when 4 h elapsed between the addition of CHI and that of TNF-alpha. Taken together, our results indicate that CHI interferes with both post-transcriptional and transcriptional repressive mechanisms of IL-8 mRNA expression.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-1179208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-1331059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-1497091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-1628615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-1856209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-2250017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-2431274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-25275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-270686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-2739725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-2771659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-3276786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-3615200,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-419694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-6330726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-685176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-7526704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-7651411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-7713192,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-7739549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-7935449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8057934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8096514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8175759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8207232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8304236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8413306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8473010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9461540-8561789
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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/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0264-6021
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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 |
330 ( Pt 1)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
429-35
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9461540-Cell Nucleus,
pubmed-meshheading:9461540-Cycloheximide,
pubmed-meshheading:9461540-DNA-Binding Proteins,
pubmed-meshheading:9461540-Epithelial Cells,
pubmed-meshheading:9461540-Gene Expression Regulation,
pubmed-meshheading:9461540-Humans,
pubmed-meshheading:9461540-Interleukin-8,
pubmed-meshheading:9461540-Lung,
pubmed-meshheading:9461540-NF-kappa B,
pubmed-meshheading:9461540-Promoter Regions, Genetic,
pubmed-meshheading:9461540-Protein Synthesis Inhibitors,
pubmed-meshheading:9461540-RNA, Messenger,
pubmed-meshheading:9461540-RNA, Neoplasm,
pubmed-meshheading:9461540-Transcription Factor AP-1,
pubmed-meshheading:9461540-Tumor Cells, Cultured,
pubmed-meshheading:9461540-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
Enhanced AP-1 and NF-kappaB activities and stability of interleukin 8 (IL-8) transcripts are implicated in IL-8 mRNA superinduction in lung epithelial H292 cells.
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pubmed:affiliation |
Department of Pulmonology, Academic Medical Centre, Meibergdreef 9, P.O. Box 22700, 110 DE Amsterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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