Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (β2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents that induce intracellular cAMP (prostaglandin...

In search of secreted protein biomarkers for the anti-inflammatory effect of β2-adrenergic receptor agonists: Application of DIGE technology in combination with multivariate and univariate data analysis tools

Two-dimensional difference gel electrophoresis (DIGE) in combination with univariate (Student's t-test) and multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to study the anti-inflammatory effects of the β2-adrenergic receptor (β2-AR) agonist zilpaterol. U937...

Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor

The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2 androgen response element. The application of this...

Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells

The effect of compounds increasing intracellular adenosine 3':5'cyclic monophosphate [cAMP](i) levels (prostacyclin. isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyrpl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied...

Synthesis, storage and regulated secretion of tissue-type plasminogen activator by cultured rat heart endothelial cells

The synthesis, storage and regulated secretion (acute release) of tissue-type plasminogen activator (tPA) were studied in cultured rat heart endothelial (RHE) cells. In this study, special attention was paid to the correspondence between tPA metabolism in RHE cells in vitro and tPA metabolism in rats in vivo. RHE cells synthetized tPA, as shown...

cGMP and nitric oxide modulate thrombin-induced endothelial permeability: Regulation via different pathways in human aortic and umbilical vein endothelial cells

Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined whether nitric oxide (NO) can serve as an...

The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor

The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 μM) were used to induce release of t-PA and vWF. The...

Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells: Effects of tumour necrosis factor α, interleukin 1 and phorbol ester

Matrix metalloproteinases (MMPs) play a role in tissue remodelling and angiogenesis. We have investigated the expression and regulation of MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin), MMP-9 (gelatinase B) and their inhibitors TIMP-1 and TIMP-2 in human umbilical vein, femoral vein and...

Pharmacological modulation of the endotoxin-induced increase in plasminogen activator inhibitor activity in rats

Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. Both the cyclooxygenase inhibitors acetylsalicylic acid and indomethacin enhanced PAI-1 induction. The combined cyclooxygenase-lipoxygenase inhibitor,...

On the role of bradykinin in secretion from vascular endothelial cells

Bradykinin will induce, in perfused rat hindlegs, the acute release from endothelial cells of tissue-type plasminogen activator and of von Willebrand factor. This release is mediated by B2-receptors, requires the influx of extracellular calcium, and is modulated by cyclic nucleotides. A possible role of bradykinin in the physiological regulation...