Vascular endothelial growth factor (VEGF) potently stimulates angiogenesis, whereas TNF-alpha has both pro- and anti-angiogenic activity. By measuring thymidine uptake, we found that TNF-alpha blocked a 2.3-fold increase in DNA synthesis induced by VEGF in human endothelial cells. To explore the possibility that the two interact to regulate endothelial cell proliferation, we examined the effect of TNF-alpha on VEGF receptor expression. In venous and arterial endothelial cells, TNF-alpha potently reduced mRNA transcripts of the two VEGF receptors (KDR/flk-1 and flt-1) in a dose- and time-dependent fashion. TNF-alpha at 1 ng/ml induced maximal inhibition of mRNA expression, which fell by approximately 70% after 24 h. TNF-alpha treatment did not significantly affect the KDR/flk-1 half-life but did decrease its rate of transcription to 40% of control. The decrease in KDR/flk-1 mRNA depended partially on new protein synthesis and was abolished by phorbol ester pretreatment. TNF-alpha decreased the amount of 35S-labeled KDR/flk-1 immunoprecipitated by an antibody specific for KDR/flk-1 to 18% of control. We conclude that TNF-alpha downregulates expression of both VEGF receptors in human endothelial cells and that this effect is transcriptional (at least for KDR/flk-1). These data support the hypothesis that TNF-alpha exerts its antiangiogenic effect in part by modulating the VEGF-specific angiogenic pathway.
C Patterson, M A Perrella, W O Endege, M Yoshizumi, M E Lee, E Haber
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IS Grewal |
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Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
2009 | |
Therapeutic Targets of the TNF Superfamily
IS Grewal |
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Therapeutic Targets of the TNF Superfamily
IS Grewal |
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Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/MSK1 signaling pathway in endothelial cells
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American journal of physiology. Cell physiology | 2004 |
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American journal of physiology. Heart and circulatory physiology | 2004 |
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Journal of Cellular Physiology | 2003 |
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European Journal of Surgical Oncology (EJSO) | 2003 |
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FEBS Letters | 2003 |
VEGF receptors are differentially expressed by neuroblastoma cells in culture
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Angiogenesis: Basic Mechanisms and Clinical Applications
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TNF-α downregulates vascular endothelial Flk-1 expression in human melanoma xenograft model
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American journal of physiology. Heart and circulatory physiology | 2003 |
Ascorbic Acid Blocks the Growth Inhibitory Effect of Tumor Necrosis Factor-α on Endothelial Cells
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Experimental biology and medicine (Maywood, N.J.) | 2003 |
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American journal of physiology. Lung cellular and molecular physiology | 2003 |
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Archives of pathology & laboratory medicine | 2003 |
Increased proliferation of endothelial cells with overexpression of soluble TNF-alpha receptor I gene
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The FASEB Journal | 2002 |
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American journal of physiology. Cell physiology | 2002 |
The New Angiotherapy
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2002 | |
Systemic Production of Vascular Endothelial Growth Factor and fms -Like Tyrosine Kinase-1 Receptor in Acute Kawasaki Disease
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Circulation | 2002 |
A novel secreted splice variant of vascular endothelial cell growth inhibitor
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The FASEB Journal | 2002 |
p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice
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Journal of Clinical Investigation | 2001 |
A Transcriptional Inhibitor of TNF-α Prevents Diabetes Induced by Multiple Low-Dose Streptozotocin Injections in Mice
M Holstad, S Sandler |
Journal of Autoimmunity | 2001 |
Bacterial Wall Products Induce Downregulation of Vascular Endothelial Growth Factor Receptors on Endothelial Cells via a CD14-Dependent Mechanism: Implications for Surgical Wound Healing
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Inflammatory Diseases of Blood Vessels
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Identification of biochemical pathways for the metabolism of oxidized low-density lipoprotein derived aldehyde-4-hydroxy trans-2-nonenal in vascular smooth muscle cells
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American journal of physiology. Heart and circulatory physiology | 2001 |
Focal Adhesion Kinase and p130Cas Mediate Both Sarcomeric Organization and Activation of Genes Associated with Cardiac Myocyte Hypertrophy
B Kovac̆ic̆-Milivojević, F Roediger, EA Almeida, CH Damsky, DG Gardner, D Ilić, MC Beckerle |
Molecular biology of the cell | 2001 |
Vascular Morphogenesis in the Female Reproductive System
HG Augustin, PA Rogers, ML Iruela-Arispe, SK Smith |
2001 | |
Altered focal adhesion regulation correlates with cardiomyopathy in mice expressing constitutively active rac1
MA Sussman, S Welch, A Walker, R Klevitsky, TE Hewett, RL Price, E Schaefer, K Yager |
Journal of Clinical Investigation | 2000 |
VEGF/Flk-1 Interaction, a Requirement for Malignant Ascites Recurrence
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Journal of Interferon & Cytokine Research | 2000 |
Enhanced proliferation and altered intracellular zinc levels in early- and late-passage mouse aorta smooth muscle cells
SK Moon, SD Ha |
Biotechnology and Bioprocess Engineering | 2000 |
Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression
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British Journal of Pharmacology | 2000 |
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Plastic & Reconstructive Surgery | 2000 |
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Kidney International | 2000 |
Laminin acts via beta 1 integrin signalling to alter cholinergic regulation of L-type Ca(2+) current in cat atrial myocytes
YG Wang, AM Samarel, SL Lipsius |
The Journal of Physiology | 2000 |
Angiogenesis in inflammatory joint disease: a target for therapeutic intervention
PE Brenchley |
Clinical & Experimental Immunology | 2000 |
Ceramide mimics tumour necrosis factor-α in the induction of cell cycle arrest in endothelial cells
R López-Marure, JL Ventura, L Sánchez, LF Montaño, A Zentella |
European Journal of Biochemistry | 2000 |
Endometrial angiogenesis
G Weston, PA Rogers |
Best Practice & Research Clinical Obstetrics & Gynaecology | 2000 |
Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1
F Vidal, J Aragonés, A Alfranca, MO de Landázuri |
Blood | 2000 |
Doxorubicin Represses CARP Gene Transcription Through the Generation of Oxidative Stress in Neonatal Rat Cardiac Myocytes: Possible Role of Serine/Threonine Kinase-dependent Pathways
Y Aihara, M Kurabayashi, T Tanaka, S Takeda, K Tomaru, K Sekiguchi, Y Ohyama, R Nagai |
Journal of Molecular and Cellular Cardiology | 2000 |
The human herpesvirus 8 homolog of Epstein-Barr virus SM protein (KS-SM) is a posttranscriptional activator of gene expression
AK Gupta, V Ruvolo, C Patterson, S Swaminathan |
Journal of virology | 2000 |
Laminin binding to beta1-integrins selectively alters beta1- and beta2-adrenoceptor signalling in cat atrial myocytes
YG Wang, AM Samarel, SL Lipsius |
The Journal of Physiology | 2000 |
Nosocomial Pneumonia
UL Specks |
Nosocomial Pneumonia | 2000 |
Homeostatic Modulation of Cell Surface KDR and Flt1 Expression and Expression of the Vascular Endothelial Cell Growth Factor (VEGF) Receptor mRNAs by VEGF
D Wang, DB Donner, RS Warren |
The Journal of biological chemistry | 2000 |
Expression of Vascular Endothelial Growth Factor Receptors in the Human Endometrium: Modulation During the Menstrual Cycle1
G Meduri, P Bausero, M Perrot-Applanat |
Biology of reproduction | 2000 |
Tumor Necrosis Factor Employs a Protein-tyrosine Phosphatase to Inhibit Activation of KDR and Vascular Endothelial Cell Growth Factor-induced Endothelial Cell Proliferation
DQ Guo, LW Wu, JD Dunbar, ON Ozes, LD Mayo, KM Kessler, JA Gustin, MR Baerwald, EA Jaffe, RS Warren, DB Donner |
The Journal of biological chemistry | 2000 |
Vascular Endothelial Growth Factor KDR Receptor Signaling Potentiates Tumor Necrosis Factor-induced Tissue Factor Expression in Endothelial Cells
BQ Shen, DY Lee, KM Cortopassi, LA Damico, TF Zioncheck |
The Journal of biological chemistry | 2000 |
Increasing endothelial cell specific expression by the use of heterologous hypoxic and cytokine-inducible enhancers
U Modlich, CW Pugh, R Bicknell |
Gene Therapy | 2000 |
Role of vascular endothelial growth factor in the regulation of angiogenesis
N Ferrara |
Kidney International | 1999 |
Vascular Endothelial Growth Factor (VEGF) and Microvessel Density in Squamous Cell Carcinomas of the Larynx: an Immunohistochemical Study
C Neuchrist |
Acta Oto-laryngologica | 1999 |
Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo
C Patterson, J Ruef, NR Madamanchi, P Barry-Lane, Z Hu, C Horaist, CA Ballinger, AR Brasier, C Bode, MS Runge |
The Journal of biological chemistry | 1999 |
Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium
F McLaughlin, B P Hayes, C M Horgan, J E Beesley, C J Campbell, A M Randi |
Cell Communication and Adhesion | 1999 |
On the Mechanism of Thrombin-induced Angiogenesis: POTENTIATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR ACTIVITY ON ENDOTHELIAL CELLS BY UP-REGULATION OF ITS RECEPTORS
NE Tsopanoglou, ME Maragoudakis |
The Journal of biological chemistry | 1999 |
The Human KDR/flk-1 Gene Contains a Functional Initiator Element That Is Bound and Transactivated by TFII-I
Y Wu, C Patterson |
The Journal of biological chemistry | 1999 |
Vascular Growth Factors and Angiogenesis
L Claesson-Welsh |
1999 | |
Inflammatory Cytokines and Vascular Endothelial Growth Factor Stimulate the Release of Soluble Tie Receptor From Human Endothelial Cells Via Metalloprotease Activation
R Yabkowitz, S Meyer, T Black, G Elliott, LA Merewether, HK Yamane |
Blood | 1999 |
Inhibition of Src Family Kinases by a Combinatorial Action of 5′-AMP and Small Heat Shock Proteins, Identified from the Adult Heart
VS Kasi, D Kuppuswamy |
Molecular and cellular biology | 1999 |
The biochemical and physiological characteristics of receptors
EP Feener, GL King |
Advanced Drug Delivery Reviews | 1998 |
Pulse treatment of human vascular endothelial cells with high doses of tumor necrosis factor and interferon-gamma results in simultaneous synergistic and reversible effects on proliferation and morphology
A Yilmaz, G Bieler, O Spertini, FJ Lejeune, C Rüegg |
International Journal of Cancer | 1998 |
Genomic structure of the human KDR/flk-1 gene
LY Yin, Y Wu, CA Ballinger, C Patterson |
Mammalian Genome | 1998 |
Vascular endothelial growth factor
I Zachary |
The International Journal of Biochemistry & Cell Biology | 1998 |
Advances in Organ Biology
AJ Liedtke |
Advances in Organ Biology | 1998 |
Angiotensin II potentiates vascular endothelial growth factor-induced angiogenic activity in retinal microcapillary endothelial cells
A Otani, H Takagi, K Suzuma, Y Honda |
Circulation research | 1998 |
Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C
A Ristimäki, K Narko, B Enholm, V Joukov, K Alitalo |
The Journal of biological chemistry | 1998 |
Transcription factors Sp1 and Sp3 alter vascular endothelial growth factor receptor expression through a novel recognition sequence
Y Hata, E Duh, K Zhang, GS Robinson, LP Aiello |
The Journal of biological chemistry | 1998 |
Increased Vascular Endothelial Growth Factor Production in the Lungs of Rats with Hypoxia-induced Pulmonary Hypertension
H Christou, A Yoshida, V Arthur, T Morita, S Kourembanas |
American journal of respiratory cell and molecular biology | 1998 |
Regulation of Vascular Endothelial Growth Factor Receptor-2 (Flk-1) Expression in Vascular Endothelial Cells
MS Pepper, SJ Mandriota |
Experimental Cell Research | 1998 |
Tumor Necrosis Factor-α Regulates Expression of Vascular Endothelial Growth Factor Receptor-2 and of Its Co-receptor Neuropilin-1 in Human Vascular Endothelial Cells
E Giraudo, L Primo, E Audero, HP Gerber, P Koolwijk, S Soker, M Klagsbrun, N Ferrara, F Bussolino |
The Journal of biological chemistry | 1998 |
Effect of TNF-α on SMIT mRNA levels and myo -inositol accumulation in cultured endothelial cells
MA Yorek, JA Dunlap, MJ Thomas, PR Cammarata, C Zhou, WL Lowe |
American journal of physiology. Cell physiology | 1998 |
Restoration of E2F Expression Rescues Vascular Endothelial Cells From Tumor Necrosis Factor- Induced Apoptosis
I Spyridopoulos, N Principe, KL Krasinski, S Xu, M Kearney, M Magner, JM Isner, DW Losordo |
Circulation | 1998 |
Genomic structure of the human KDR/flk-1 gene.
Yin LY, Wu Y, Ballinger CA, Patterson C |
Mammalian genome : official journal of the International Mammalian Genome Society | 1998 |
Arterial Wall Neovascularization
K Pels, M Labinaz, ER O'Brien |
Japanese Circulation Journal | 1997 |
Halting angiogenesis suppresses carcinoma cell invasion
M Skobe, P Rockwell, N Goldstein, S Vosseler, NE Fusenig |
Nature Medicine | 1997 |
Interference with c-myc Expression and RB Phosphorylation during TNF-Mediated Growth Arrest in Human Endothelial Cells
R López-Marure, AE Bernal, A Zentella |
Biochemical and Biophysical Research Communications | 1997 |
Side effects of cancer treatment with recombinant human tumour necrosis factor alpha: a new challenge for the intensive care unit
JH Zwaveling, JK Maring, AR Giribes, HS Koops |
Clinical Intensive Care | 1997 |
The Biology of Vascular Endothelial Growth Factor
N Ferrara, T Davis-Smyth |
Endocrine reviews | 1997 |
The Genetics of Cancer
BA Ponder, MJ Waring |
The Genetics of Cancer | 1995 |