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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2000-12-18
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pubmed:abstractText |
Interleukin 1beta (IL-1beta) is a multifunctional polypeptide considered a key cytokine during inflammation. Fibronectin (FN), a matrix glycoprotein highly expressed in injured tissues, can induce expression of IL-1beta in human blood monocytic cells. Herein, we explore the intracellular signals and transcriptional mechanisms responsible for IL-1beta induction by FN using human promonocytic U937 cells transfected with the human IL-1beta promoter connected to a reporter gene. Exposure of transfected U937s to FN resulted in increased expression of the full-length IL-1beta promoter. This effect, mediated via the alpha5beta1 integrin, was associated with activation of mitogen-activated protein kinases (MAPKs) and was abolished by pre-treatment of cells with Calphostin C, a specific inhibitor of protein kinase C (PKC) activation. Deletion analysis and co-transfection studies using consensus activator protein 1 (AP-1) oligonucleotides suggested that an AP-1 site present in the 5' end of the IL-1beta promoter was involved in the FN-induced response. Finally, electrophoretic mobility shift assays showed that FN induced binding of AP-1, but not NF-kappaB. Together, these experiments demonstrate that FN binding to the alpha5beta1 integrin activates MAPK-dependent signal pathways, and results in the transcription of the IL-1beta promoter in U937 cells by activating PKC and inducing AP-1.
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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/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fibronectin,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/arginyl-glycyl-aspartic acid,
http://linkedlifedata.com/resource/pubmed/chemical/calphostin C
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1043-4666
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1581-96
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11052809-Blotting, Northern,
pubmed-meshheading:11052809-Blotting, Western,
pubmed-meshheading:11052809-Cell Adhesion,
pubmed-meshheading:11052809-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:11052809-Dose-Response Relationship, Drug,
pubmed-meshheading:11052809-Electroporation,
pubmed-meshheading:11052809-Enzyme Activation,
pubmed-meshheading:11052809-Enzyme Inhibitors,
pubmed-meshheading:11052809-Fibronectins,
pubmed-meshheading:11052809-Gene Deletion,
pubmed-meshheading:11052809-Gene Expression Regulation,
pubmed-meshheading:11052809-Genes, Reporter,
pubmed-meshheading:11052809-Humans,
pubmed-meshheading:11052809-Interleukin-1,
pubmed-meshheading:11052809-Lipopolysaccharides,
pubmed-meshheading:11052809-MAP Kinase Signaling System,
pubmed-meshheading:11052809-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11052809-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:11052809-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11052809-NF-kappa B,
pubmed-meshheading:11052809-Naphthalenes,
pubmed-meshheading:11052809-Oligopeptides,
pubmed-meshheading:11052809-Precipitin Tests,
pubmed-meshheading:11052809-Promoter Regions, Genetic,
pubmed-meshheading:11052809-Protein Kinase C,
pubmed-meshheading:11052809-RNA, Messenger,
pubmed-meshheading:11052809-Receptors, Fibronectin,
pubmed-meshheading:11052809-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11052809-Signal Transduction,
pubmed-meshheading:11052809-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11052809-Transcription, Genetic,
pubmed-meshheading:11052809-Transcription Factor AP-1,
pubmed-meshheading:11052809-Transfection,
pubmed-meshheading:11052809-U937 Cells
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pubmed:year |
2000
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pubmed:articleTitle |
Transcriptional regulation of the human interleukin 1beta gene by fibronectin: role of protein kinase C and activator protein 1 (AP-1).
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pubmed:affiliation |
Pulmonary and Critical Care Division, Department of Medicine, Atlanta Veterans Affairs Medical Center and Emory University School of Medicine, Atlanta, Georgia, USA. roman-rodriguez.jesse@atlanta.va.gov
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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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