|
|
 Previous Article | Table of Contents | Next Article 
Tumor necrosis factor-alpha downregulates protein S secretion in human
microvascular and umbilical vein endothelial cells but not in the HepG- 2
hepatoma cell line
WC Hooper, DJ Phillips, MJ Ribeiro, JM Benson, VG George, EW Ades and BL Evatt
Hematologic Diseases Branch, Centers for Disease Control and Prevention,
Altanta, GA 30333.
Protein S deficiency, which is associated with thrombosis, can either be
inherited or acquired. Recently, we reported that a decrease in free
protein S was observed in 19 of 25 persons with HIV/AIDS. The
proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been
reported to be elevated in human immunodeficiency virus (HIV)/acquired
immunodeficiency syndrome (AIDS) patients and has been shown to induce a
procoagulant state on the surface of endothelial cells. We report here that
recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the
SV-40T transfected human microvascular endothelial cell line (HMEC-1) model
system by approximately 70% and in primary human umbilical vein and dermal
microvascular endothelial cell cultures by approximately 50%. Using the
HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at
24 hours that was corroborated by Western blot analysis and enzyme- linked
immunosorbent assay (ELISA) quantification. Evidence supporting the
specificity of the TNF-alpha effect included the following: (1) TNF- alpha
down-regulation of protein S was completely blocked by TNF neutralizing
antibody; (2) the effect was transient, and protein S was restored to near
normal levels after TNF was removed from cell cultures; (3) an antibody
directed to the TNF RI (55-kD receptor) was shown to mimic the action of
TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines,
interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S
secretion. However, TNF-alpha showed no regulatory control over protein S
synthesis in the human hepatocellular carcinoma cell line HepG-2. We
suggest that TNF-alpha downregulation of protein S may be a mechanism for
localized procoagulant activity and thrombosis recently reported in some
AIDS patients with associated protein S deficiency.
Volume 84,
Issue 2,
pp. 483-489,
07/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
W. M. Lijfering, H. G. Sprenger, R. R. Georg, P. A. van der Meulen, and J. van der Meer
Relationship between Progression to AIDS and Thrombophilic Abnormalities in HIV Infection
Clin. Chem.,
July 1, 2008;
54(7):
1226 - 1233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Mochan, M Modi, and G Modi
Protein S deficiency in HIV associated ischaemic stroke: an epiphenomenon of HIV infection
J. Neurol. Neurosurg. Psychiatry,
October 1, 2005;
76(10):
1455 - 1456.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mochan, M. Modi, and G. Modi
Stroke in Black South African HIV-Positive Patients: A Prospective Analysis
Stroke,
January 1, 2003;
34(1):
10 - 15.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. McLaughlin, V. J. Ludbrook, J. Cox, I. von Carlowitz, S. Brown, and A. M. Randi
Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation
Blood,
December 1, 2001;
98(12):
3332 - 3339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F McLaughlin, V. Ludbrook, I Kola, C. Campbell, and A. Randi
Characterisation of the tumour necrosis factor (TNF)-(alpha) response elements in the human ICAM-2 promoter
J. Cell Sci.,
January 12, 1999;
112(24):
4695 - 4703.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. C. Hooper, D. J. Phillips, M. A. Renshaw, B. L. Evatt, and J. M. Benson
The Up-Regulation of IL-6 and IL-8 in Human Endothelial Cells by Activated Protein C
J. Immunol.,
September 1, 1998;
161(5):
2567 - 2573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. van der Poll, S. M. Coyle, M. Levi, P. M. Jansen, M. Dentener, K. Barbosa, W. A. Buurman, C. E. Hack, J. W. ten Cate, J. M. Agosti, et al.
Effect of a Recombinant Dimeric Tumor Necrosis Factor Receptor on Inflammatory Responses to Intravenous Endotoxin in Normal Humans
Blood,
May 15, 1997;
89(10):
3727 - 3734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Conway, L. Liu, B. Nowakowski, M. Steiner-Mosonyi, S. P. Ribeiro, and M. Michalak
Heat Shock-sensitive Expression of Calreticulin
J. Biol. Chem.,
July 14, 1995;
270(28):
17011 - 17016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
