Respiratory irritation associated with inhalation of boron trifluoride and fluorosulfonic acid

The objectives of this study were to examine the respiratory irritancy of boron trifluoride (BF3) and fluorosulfonic acid (FSA) following acute inhalation exposure. Testing was conducted using groups of 10 male and 10 female rats (BF3) or groups of 6 male rats (FSA). Rats were exposed for a single 4-h period (BF3) or a single 1-h period (FSA)...

Huidblootstelling is een risico voor luchtwegallergie

Beroepsastma en andere luchtwegallergieën komen veel voor. Het aantal allergieveroorzakende stoffen is namelijk groot en neemt nog altijd toe. Goede testmethoden om luchtwegallergieën op te sporen zijn daarom gewild. Ze zijn helaas ook moeilijk te ontwikkelen. TNO denkt echter een goede teststrategie gevonden te hebben. De dierproeven...

On the role of c-Jun in the induction of PAI-1 gene expression by phorbol ester, serum, and IL-1α in HepG2 cells

We have characterized the regulation of plasminogen activator inhibitor- 1 (PAI-1) gene expression by phorbol 12-myristate 13-acetate (PMA), serum, and interleukin-1α (IL-1α) in the human hepatoma cell line HepG2. PMA, serum, and IL-1α induced a rapid and transient 28-fold (PMA), 9-fold (serum), and 23-fold (IL-1α) increase in PAI-1 mRNA,...

Cell-type specific DNA-protein interactions at the tissue-type plasminogen activator promoter in human endothelial and HeLa cells in vivo and in vitro

Tissue-type plasminogen activator (t-PA) gene expression in human endothelial cells and HeLa cells is stimulated by the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) at the level of transcription. To study the mechanism of transcriptional regulation, we have characterized a segment of the t-PA gene extending from -135 to +100...

Studies on the mechanism of fibrate-inhibited expression of plasminogen activator inhibitor-1 in cultured hepatocytes from cynomolgus monkey

Fibrates are widely used drugs in hyperlipidemic disorders. In addition to lowering serum triglyceride levels, fibrates have also been shown to reduce elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels in vivo. We demonstrate that fibrates suppress PAI-1 synthesis in cultured cynomolgus monkey hepatocytes in a concentration...

Role of c-Jun and proximal phorbol 12-myristate-13-acetate-(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-1 gene expression in HepG2

Experiments were designed to clarify the role of c-Jun/c-Fos and of putative phorbol 12-myristate-13-acetate-(PMA)-responsive elements (TREs) in the induction of plasminogen-activator inhibitor 1 (PAI-1) gene transcription in the human hepatoma cell line HepG2 by activators of protein kinase C (PKC). Treatment of HepG2 cells with the phorbol...

Aspects of T-PA and PAI-1 gene regulation in human endothelial cells and hepatocytes

Stimulation of tissue-type plasminogen activator gene expression by sodium butyrate and trichostatin A in human endothelial cells involves histone acetylation

We have previously shown that the pleiotropic agent sodium butyrate strongly stimulates tissue-type plasminogen activator (t-PA) expression in human umbilical vein endothelial cells (HUVEC). Here we provide the following evidence that the butyrate-induced t-PA expression in HUVEC involves histone H4 acetylation. (1) t-PA induction by butyrate...

Regulation of endothelial cell t-PA synthesis and release

The fibrinolytic activity of blood is to a large extent determined by the plasma level of tissue-type plasminogen activator (t-PA). Changes in the plasma level of t-PA are mainly achieved by the endothelium by two mechanisms: (a) a rapid, short-term release of t-PA, which occurs within minutes (acute release, regulated secretion) and (b) a long...