Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-4-7
pubmed:abstractText
We examined the regulation by tumor necrosis factor-alpha (TNF alpha) of plasminogen activator inhibitor-1 (PAI-1) in cultured peritubular cells recovered from 20-day-old rat testes. We demonstrated that TNF alpha in a nanomolar dose range stimulated PAI-1 messenger RNA (mRNA; Northern blots) as well as immunoreactive (Western blots) and bioactive (Stachrom) PAI-1 protein. Induction of PAI-1 mRNA started 4 h after the addition of TNF alpha (2.5-fold increase) and peaked (7-fold increase) after 24 h of treatment. Actinomycin D and cycloheximide inhibited the effects of TNF alpha on PAI-1 mRNA, suggesting that ongoing RNA and protein syntheses were required. The combined actions of transforming growth factor-alpha (TGF alpha), a potent inducer of PAI-1, and TNF alpha on PAI-1 were less than additive, suggesting the activation of some common pathway. TNF alpha action on PAI-1, like that of TGF alpha demonstrated previously, was masked by a preexposure to phorbol myristate acetate (a stimulator of protein kinase C) and strongly reduced by staurosporine (an inhibitor of the protein kinase C). Furthermore, using genistein to inhibit tyrosine kinase activity, we not only blocked the action of TGF alpha on PAI-1 [initiated upon binding to the tyrosine kinase epidermal growth factor/TGF alpha receptor (EGFR)], but also markedly reduced that of TNF alpha. Finally, TNF alpha, at a dose range that stimulated PAI-1, enhanced EGFR mRNA levels and EGF binding. Together, the present findings suggest that some of the biological effects of TNF alpha on PAI-1 might be secondary to de novo synthesis of EGFR. Because TNF alpha probably originates from testicular macrophages, such a regulation of PAI-1 by TNF alpha may occur in the context of physiological interactions between the testis and the immune system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Genistein, http://linkedlifedata.com/resource/pubmed/chemical/Isoflavones, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1, http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1097-105
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9048615-Animals, pubmed-meshheading:9048615-Cells, Cultured, pubmed-meshheading:9048615-Cycloheximide, pubmed-meshheading:9048615-Dactinomycin, pubmed-meshheading:9048615-Enzyme Inhibitors, pubmed-meshheading:9048615-Epidermal Growth Factor, pubmed-meshheading:9048615-Genistein, pubmed-meshheading:9048615-Isoflavones, pubmed-meshheading:9048615-Male, pubmed-meshheading:9048615-Plasminogen Activator Inhibitor 1, pubmed-meshheading:9048615-Protein Synthesis Inhibitors, pubmed-meshheading:9048615-RNA, Messenger, pubmed-meshheading:9048615-Rats, pubmed-meshheading:9048615-Receptor, Epidermal Growth Factor, pubmed-meshheading:9048615-Staurosporine, pubmed-meshheading:9048615-Testis, pubmed-meshheading:9048615-Tetradecanoylphorbol Acetate, pubmed-meshheading:9048615-Transforming Growth Factor alpha, pubmed-meshheading:9048615-Tumor Necrosis Factor-alpha, pubmed-meshheading:9048615-Up-Regulation
pubmed:year
1997
pubmed:articleTitle
Tumor necrosis factor-alpha regulates plasminogen activator inhibitor-1 in rat testicular peritubular cells.
pubmed:affiliation
INSERM U-407, Batiment 3B, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't