Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
|
| pubmed:dateCreated |
1994-11-28
|
| pubmed:abstractText |
Differential expression of PAI-1 in connective tissues has been associated etiologically with some forms of arthritis. Our objective was to delineate the mechanisms by which PGE2 and IL-1 beta, inflammatory mediators commonly found at sites of inflammation, regulate the expression and synthesis of PAI-1 in human synoviocytes. PGE2 (and PGE1) inhibited PAI-1 mRNA expression and secretion in a dose-dependent manner with an IC50 (for antigen secretion) of 4.6 x 10(-10) M and 8.7 x 10(-10) M, respectively. Cyclic AMP agonists forskolin, Sp-cAMP, and IBMX mimic the effects of the PGEs. rhIL-1 beta stimulated the secretion of PAI-1 in a dose-dependent fashion under basal culture conditions; the effect was reversed by actinomycin D and the protein kinase inhibitors H7 and staurosporine but not KT-5720. PMA, an activator of protein kinase C, transiently increased (maximum 3 h) the expression of PAI-1 mRNA by approximately 10-fold, especially the 3.2 kb species. However, there was no significant increase in PAI-1 antigen secreted into the culture medium after PMA (100-300 nM) treatment. The half-life (t1/2) of PAI-1 mRNA, both the 3.2 and 2.2 transcripts was about 9.6 h (mean n = 3) and PGE2 has no affect on the stability of both messages. PGE2 reduced the rate of PAI-1 gene transcription as judged by run-off assays. The NSAID naproxen (30 micrograms/ml) induced the expression of PAI-1 mRNA over basal levels and super-induced the inhibitor's expression above rhIL-1 beta stimulated levels. Our results suggest that PGE2 suppresses PAI-1 expression and synthesis by activation of the cAMP/PKA system and inhibition of the rate of gene transcription. Data concerning the activation of PKC suggest that the expression, synthesis and release of the PAI-1 may be differentially regulated in normal human synoviocytes.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0303-7207
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
103
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
139-48
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7525383-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:7525383-Blood,
pubmed-meshheading:7525383-Cadaver,
pubmed-meshheading:7525383-Cells, Cultured,
pubmed-meshheading:7525383-Culture Media,
pubmed-meshheading:7525383-Cyclic AMP,
pubmed-meshheading:7525383-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:7525383-Dinoprostone,
pubmed-meshheading:7525383-Fibroblasts,
pubmed-meshheading:7525383-Forskolin,
pubmed-meshheading:7525383-Gene Expression Regulation,
pubmed-meshheading:7525383-Humans,
pubmed-meshheading:7525383-Interleukin-1,
pubmed-meshheading:7525383-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:7525383-Protein Kinase Inhibitors,
pubmed-meshheading:7525383-RNA, Messenger,
pubmed-meshheading:7525383-Synovial Membrane,
pubmed-meshheading:7525383-Tetradecanoylphorbol Acetate,
pubmed-meshheading:7525383-Transcription, Genetic
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Transcriptional regulation of plasminogen activator inhibitor-1 expression in human synovial fibroblasts by prostaglandin E2: mediation by protein kinase A and role of interleukin-1.
|
| pubmed:affiliation |
Department of Medicine, University of Montreal, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|