Synergistic induction of apoptosis in human endothelial cells by tumour necrosis factor-alpha and transforming growth factor-beta.
Serum deprivation stimulates endothelial apoptosis while albumin inhibits this and has been proposed as important in confining apoptotic remodelling to poorly perfused vessels. Tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta are also reported to induce endothelial apoptosis. To investigate the comparative roles of these stimuli, the effect of TNF-alpha and TGF-beta, alone or in combination, in the presence or absence of serum or albumin was studied. There was strong synergy between the cytokines in inducing human umbilical vein endothelial cell apoptosis, but only in the absence of serum. Synergy was destroyed by boiling cytokines and was not affected by polymyxin B. Dose response experiments revealed greater activity of TGF-beta(1) than TGF-beta(2). The synergy was protein synthesis dependent and apoptosis was confirmed by DNA gel electrophoresis, transmission electron microscopy and FACS analysis. Data suggests a role for synergistic activation of endothelial cell apoptosis by TNF-alpha and TGF-beta(1) but perhaps only in poorly perfused vessels deprived of serum factors.
Emmanuel
Catherine
C
Cellular and Molecular Pathology Research Unit, Department of Oral Medicine and Oral Pathology, University of Sydney, Australia. cathye@dental.wsahs.nsw.gov.au
Foo
Eugene
E
Medbury
Heather J
HJ
Matthews
Janice
J
Comis
Alfio
A
Zoellner
Hans
H
D017209:Apoptosis; D002469:Cell Separation; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008854:Microscopy, Electron; D010477:Perfusion; D011112:Polymyxin B / Q000494:pharmacology; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D016207:Cytokines; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D011112:Polymyxin B