Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.

Nauck, Markus; Roth, Michael; Tamm, Michael; Eickelberg, Oliver; Wieland, Heinrich; Stulz, P; Perruchoud, André P.

doi:10.1165/ajrcmb.16.4.9115750

Cited by 204 publications

(113 citation statements)

References 42 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Immunohistochemistry-Expression of GR and ␤ 2 -AR by fibroblasts or VSMC was assessed by immunohistochemistry, as described previously (22). Cells were seeded onto 8-well chamber slides at 80% confluency and growth-arrested for 24 h. After washing three times with ice-cold phosphate-buffered saline (PBS), cells were fixed in PBS containing 4% formaldehyde.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Ligand-independent Activation of the Glucocorticoid Receptor by β2-Adrenergic Receptor Agonists in Primary Human Lung Fibroblasts and Vascular Smooth Muscle Cells

Eickelberg

Roth

Lörx

et al. 1999

Journal of Biological Chemistry

364

208

View full text Add to dashboard Cite

The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor present in most cell types. Upon ligand binding, the GR is activated and translocates into the nucleus where it transmits the anti-inflammatory actions of glucocorticoids. Here, we describe the ligand-independent activation of GR by the ␤ 2 -adrenergic receptor (␤ 2 -AR) agonists, salbutamol and salmeterol, in primary human lung fibroblasts and vascular smooth muscle cells. Immunohistochemistry demonstrated expression of GR and the ␤ 2 -AR by fibroblasts and vascular smooth muscle cells. Treatment of the cells with the ␤ 2 -AR agonists, salbutamol or salmeterol, resulted in translocation of GR into the nucleus beginning at 30 min, as shown by immunohistochemistry and Western blotting of cytosolic and nuclear cell extracts. In comparison, activation of GR induced by the corticosteroids dexamethasone and fluticasone occurred at the same time after treatment (30 min) but resulted in a more complete depletion of GR from the cytosolic compartment. Electrophoretic mobility shift assays confirmed that nuclear GR, activated by both ␤ 2 -AR agonists and glucocorticoids, actively bound to the GR consensus sequence (GR element). Functional activation of the GR was confirmed by a Luciferase reporter gene assay, using a GR driven promoter fragment from the p21 (WAF1/CIP1) gene. The effects of the ␤ 2 -AR agonists, salbutamol and salmeterol, were dependent upon binding to the ␤ 2 -AR, because blocking of ␤ 2 -AR with propranolol abrogated GR activation. GR activation appeared to involve cAMP. In summary, these data show that ␤ 2 -AR agonists are potent activators of GR. Ligandindependent activation of GR by ␤ 2 -AR agonists may substantially mediate the anti-inflammatory actions of these drugs observed in vitro and in vivo.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Unspecific binding of the secondary antibody was examined by following the outlined protocol, without the addition of primary antibodies. Cells were counterstained with Mayer's hemalum (22).…”

Section: Methodsmentioning

confidence: 99%

Ligand-independent Activation of the Glucocorticoid Receptor by β2-Adrenergic Receptor Agonists in Primary Human Lung Fibroblasts and Vascular Smooth Muscle Cells

Eickelberg

Roth

Lörx

et al. 1999

Journal of Biological Chemistry

364

208

View full text Add to dashboard Cite

show abstract

“…As an example, in lung no variations in VEGF expression were found (4), whereas several in vitro studies showed that dexamethasone strongly downregulates and/or inhibits induction of VEGF (34,46). However, in rat glioma cells, it has been shown that dexamethasone induced a differential downregulation of VEGF under normoxic and hypoxic conditions (29).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

Mallet

Féraud²,

Ouengue-Mbélé

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Mallet, Christine, Olivier Fé raud, Gaehl OuengueMbé lé , Isabelle Gaillard, Nicolas Sappay, Daniel Vittet, and Isabelle Vilgrain. Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH. Am J Physiol Endocrinol Metab 284: E156-E167, 2003; 10.1152/ajpendo.00450.2001.-Although ACTH is important to adrenal growth and steroidogenesis, its role in vascular development and function has not been established in vivo. In the present study, we demonstrate the expression of mRNA for all four VEGF isoforms (mVEGF120, 144, 164, 188) and for Flk-1/KDR and Flt-1 receptors in the mouse adrenal in vivo. Suppression of the pituitary adrenocortical axis by dexamethasone (0.5 mg ⅐ 100 g body wt Ϫ1 ⅐ day Ϫ1 during 6 days) induced a decrease in corticosterone levels, adrenal weights by 50% (P Ͻ 0.001), VEGF188 mRNA, and Flk-1/KDR mRNA, whereas Flt-1 remained consistent during steroid treatment. A daily injection of ACTH-(1-39) restored the transcript for Flk-1/KDR and both VEGF188 and plasma corticosterone to control levels. To gain further insights into the effects of ACTH, cultured endothelial cells (ECs) were treated with forskolin, which increases cAMP, the second messenger in ACTH action. We demonstrate that Flk-1/KDR protein expression was markedly increased by forskolin within 24-48 h of treatment in a dose-dependent manner (0.1-10 M). The biological effect of ACTH on ECs was then tested by use of coincubations of fasciculata cells and ECs in 3D-collagen assay. Within 5-7 days of culture, ECs organized into multicellular structures that resemble networks of microvasculature, which characterize angiogenesis in vitro. vascular endothelial growth factor receptors; adrenocorticotropin; angiogenesis; mouse adrenal; steroidogenesis; hypothalamo-pituitary disconnection; vascular permeability THE ADRENAL CORTEX is physiologically important as the site of formation and secretion of several steroid hormones and less-active steroids. The secreted hormones gain access to the bloodstream through an intense and complex adrenal vasculature that is essential for organ growth and maintenance. The vessels of the adrenal cortex are characterized by richly fenestrated endothelia (2, 40). These fenestrations are the pores through which releasing factors within the hemal milieu can access the cells. In adult mammals, adrenal growth and steroidogenesis are regulated by adrenocorticotropin (ACTH) (27), which acts through interaction with a specific melanocortin receptor (MC2R) specifically expressed in the adrenal cortex (6, 32). This guanine nucleotide-binding protein-coupled receptor elicits the activation of adenylate cyclase and the production of cAMP, which activate the protein kinase A-signaling pathway (39, 53) and the normal functioning of adrenocortical cells. Glucocorticoid hormones are thought to exert negative feedback inhibition on hypothalamic-pituitary-adrenocortical axis activity at the pituitary, hypothalamic, and extrahypothalamic levels. This ultimately results in decreased...

show abstract

“…Many in vitro studies (Nauck et al, 1997;Nauck et al, 1998;Harada et al, 1994;Tanabe et al, 2006) have described a strong negative regulation of the induction of VEGF expression by dexamethasone in different cell types, including alveolar epithelial cells.…”

Section: Effects Of Betamethasone Vs Dexamethasone On the Expression mentioning

confidence: 99%

Effects of Oxidative Stress and Antenatal Corticosteroids on the Pulmonary Expression of Vascular Endothelial Growth Factor (VEGF) and Alveolarization

Remesal¹,

Feliciano²,

Ludeña³

2012

Oxidative Stress - Molecular Mechanisms and Biological Effects

View full text Add to dashboard Cite

Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.

Cited by 204 publications

References 42 publications

Ligand-independent Activation of the Glucocorticoid Receptor by β2-Adrenergic Receptor Agonists in Primary Human Lung Fibroblasts and Vascular Smooth Muscle Cells

Ligand-independent Activation of the Glucocorticoid Receptor by β2-Adrenergic Receptor Agonists in Primary Human Lung Fibroblasts and Vascular Smooth Muscle Cells

Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

Effects of Oxidative Stress and Antenatal Corticosteroids on the Pulmonary Expression of Vascular Endothelial Growth Factor (VEGF) and Alveolarization

Contact Info

Product

Resources

About