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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-10-23
pubmed:abstractText
Type-1 plasminogen activator inhibitor (PAI-1), the major regulator of fibrinolysis, is an important component of the acute phase (AP) response, the coordinated systemic reaction of an organism to tissue injury. As part of a combined in vivo and in vitro study of AP regulation of PAI-1 gene expression in murine hepatocytes, we have characterized the cytokine regulation of PAI-1 gene expression in AML 12 cells, an established line of normal hepatocytes derived from an adult transgenic mouse overexpressing transforming growth factor alpha. Interleukin (IL)-1 caused a rapid and transient 4-fold increase in PAI-1 mRNA that was maximal at 1 h. Half-maximal induction by IL-1 was obtained at 50 U/ml and maximal effects were seen at approximately 500 U/ml. Tumor necrosis factor alpha induced PAI-1 mRNA accumulation with the same magnitude and time course as IL-1, and was not additive with IL-1. IL-6 and dexamethasone alone had no effect on PAI-1 mRNA accumulation and did not enhance the effect of IL-1. Transforming growth factor beta caused a sustained 5- to 7-fold increase in the accumulation of PAI-1 mRNA that was maximal after 2 to 4 h. The IL-1 induction of PAI-1 was inhibited by actinomycin D, but not by cycloheximide. Nuclear run-on studies demonstrated that IL-1 induced a rapid and transient increase in PAI-1 gene transcription that was maximal at 30 min. IL-1 did not stabilize PAI-1 mRNA, and might, in fact, accelerate its rate of decay. These data demonstrate that IL-1, a potent mediator of AP response, induces the accumulation of PAI-1 mRNA in murine hepatocytes, at least in part, by rapidly and transiently increasing the rate of transcription of the PAI-1 gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
648-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12.
pubmed:affiliation
Department of Human Genetics, The University of Michigan Medical School, Ann Arbor 48109-0618, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.