Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:612-621
© 1995 American Heart Association, Inc.
Articles |
Transcriptional Regulation of Tissue Factor Expression in Human Endothelial Cells
From the Department of Immunology, The Scripps Research Institute, La Jolla, Calif.
Correspondence to Nigel Mackman, PhD, The Scripps Research Institute, 10666 N Torrey Pines Rd, IMM-17, La Jolla, CA 92037.
Abstract Tissue factor (TF) expression by endothelial cells
is implicated in thrombotic episodes in patients with a variety of
clinical disorders. In a baboon model of lethal sepsis, TF is expressed
by endothelial cells in the splenic microvasculature. In vitro,
endothelial cells are induced to express TF in response to tumor
necrosis factor–
(TNF-), interleukin-1ß (IL-1ß), and
bacterial endotoxin (lipopolysaccharide [LPS]). Here, we identified
cis-acting regulatory elements that control TF gene
transcription in primary human endothelial cells. Functional
studies showed that the TF promoter contained a 56-bp enhancer
(-227 to -172 bp), which included two activator protein–1 (AP-1)
sites and a 
B-like site, that mediated induction by TNF-,
IL-1ß, and LPS. Electrophoretic mobility shift assays demonstrated
that endothelial cells contained constitutive AP-1 binding activity,
whereas the B-like site, 5'-CGGAGTTTCC-3', bound an inducible
nuclear complex composed of c-Rel–p65 heterodimers. Taken together,
our data suggest that induction of TF gene transcription in endothelial
cells is mediated by functional interactions between Fos-Jun and
c-Rel–p65 heterodimers.
Key Words: endothelium • tissue factor • gene expression
This article has been cited by other articles:
 |
|
 |
|
  R. S. Kasthuri, M. B. Taubman, and N. Mackman Role of Tissue Factor in Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4834 - 4838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Deng, J. P. Luyendyk, P. E. Ganey, and R. A. Roth Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models Pharmacol. Rev., September 1, 2009; 61(3): 262 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, S. A. Mahmud, P. B. Bitterman, Y. Huo, and A. Slungaard Histone Deacetylase Inhibitors Suppress TF-{kappa}B-dependent Agonist-driven Tissue Factor Expression in Endothelial Cells and Monocytes J. Biol. Chem., September 28, 2007; 282(39): 28408 - 28418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mackman, R. E. Tilley, and N. S. Key Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1687 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Luyendyk, J. D. Piper, M. Tencati, K. V. Reddy, T. Holscher, R. Zhang, J. Luchoomun, X. Chen, W. Min, C. Kunsch, et al. A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hamik, Z. Lin, A. Kumar, M. Balcells, S. Sinha, J. Katz, M. W. Feinberg, R. E. Gerszten, E. R. Edelman, and M. K. Jain Kruppel-like Factor 4 Regulates Endothelial Inflammation J. Biol. Chem., May 4, 2007; 282(18): 13769 - 13779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-Y. Chong and G. Y.H. Lip Viewpoint: The prothrombotic state in heart failure: A maladaptive inflammatory response? Eur J Heart Fail, February 1, 2007; 9(2): 124 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty and K. I. Block Toward a Core Nutraceutical Program for Cancer Management Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Eto, A. Kouroedov, F. Cosentino, and T. F. Luscher Glycogen Synthase Kinase-3 Mediates Endothelial Cell Activation by Tumor Necrosis Factor-{alpha} Circulation, August 30, 2005; 112(9): 1316 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hezi-Yamit, P. W. Wong, N. Bien-Ly, L. G. Komuves, K. S. S. Prasad, D. R. Phillips, and U. Sinha Synergistic induction of tissue factor by coagulation factor Xa and TNF: Evidence for involvement of negative regulatory signaling cascades PNAS, August 23, 2005; 102(34): 12077 - 12082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Sohn, C. B. Deming, D. C. Johns, H. C. Champion, C. Bian, K. Gardner, and J. J. Rade Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B Blood, May 15, 2005; 105(10): 3910 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Franscini, E. B. Bachli, N. Blau, M.-S. Leikauf, A. Schaffner, and G. Schoedon Gene Expression Profiling of Inflamed Human Endothelial Cells and Influence of Activated Protein C Circulation, November 2, 2004; 110(18): 2903 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, K. Pelekanakis, and M. J. Woolkalis Thrombin and Tumor Necrosis Factor {alpha} Synergistically Stimulate Tissue Factor Expression in Human Endothelial Cells: REGULATION THROUGH c-Fos AND c-Jun J. Biol. Chem., August 20, 2004; 279(34): 36142 - 36147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sharma, E. Melis, M. J. Hickey, C. D. Clyne, J. Erlich, L. M. Khachigian, P. Davenport, E. Morand, P. Carmeliet, and P. G. Tipping The Cytoplasmic Domain of Tissue Factor Contributes to Leukocyte Recruitment and Death in Endotoxemia Am. J. Pathol., July 1, 2004; 165(1): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takeya, E. C. Gabazza, S. Aoki, H. Ueno, and K. Suzuki Synergistic effect of sphingosine 1-phosphate on thrombin-induced tissue factor expression in endothelial cells Blood, September 1, 2003; 102(5): 1693 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Philipp, A. Dienst, M. Unruh, A. Wagener, A. Grunow, A. Engert, J. W.U. Fries, and C. Gottstein Soluble Tissue Factor Induces Coagulation on Tumor Endothelial Cells In Vivo if Coadministered With Low-Dose Lipopolysaccharides Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 905 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Siflinger-Birnboim and A. Johnson Protein kinase C modulates pulmonary endothelial permeability: a paradigm for acute lung injury Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L435 - L451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Webster Editorial III: Inflammation and the coagulation system Br. J. Anaesth., August 1, 2002; 89(2): 216 - 220. [Full Text] [PDF]
|
|
|
|
|
|
U. Bavendiek, P. Libby, M. Kilbride, R. Reynolds, N. Mackman, and U. Schonbeck Induction of Tissue Factor Expression in Human Endothelial Cells by CD40 Ligand Is Mediated via Activator Protein 1, Nuclear Factor kappa B, and Egr-1 J. Biol. Chem., July 5, 2002; 277(28): 25032 - 25039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Loewe, W. Holnthoner, M. Groger, M. Pillinger, F. Gruber, D. Mechtcheriakova, E. Hofer, K. Wolff, and P. Petzelbauer Dimethylfumarate Inhibits TNF-Induced Nuclear Entry of NF-{kappa}B/p65 in Human Endothelial Cells J. Immunol., May 1, 2002; 168(9): 4781 - 4787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kottke-Marchant and S. Sapatnekar Hemostatic Abnormalities in Cardiopulmonary Bypass: Pathophysiologic and Transfusion Considerations Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2001; 5(3): 187 - 206. [Abstract] [PDF]
|
|
|
|
|
|
N. Wang, L. Verna, H.-l. Liao, A. Ballard, Y. Zhu, and M. B. Stemerman Adenovirus-Mediated Overexpression of Dominant-Negative Mutant of c-Jun Prevents Intercellular Adhesion Molecule-1 Induction by LDL: A Critical Role for Activator Protein-1 in Endothelial Activation Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1414 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Holschermann, C. Rascher, C. Oelschlager, G. Stapfer, A. Langenstein, A. Staubitz, U. Maus, H. Tillmanns, H. Bang, and W. Haberbosch Opposite Regulation of Tissue Factor Expression by Calcineurin in Monocytes and Endothelial Cells J. Immunol., June 15, 2001; 166(12): 7112 - 7120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishibe, G. Parry, A. Ishida, S. Aziz, J. Murray, Y. Patel, S. Rahman, K. Strand, K. Saito, Y. Saito, et al. Oncostatin M promotes biphasic tissue factor expression in smooth muscle cells: evidence for Erk-1/2 activation Blood, February 1, 2001; 97(3): 692 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Gil Inflammo-coagulatory response, extrinsic pathway thrombin generation and a new theory of activated clotting time interpretation Perfusion, January 1, 2001; 16(1): 27 - 35. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Maderna, C. Godson, G. Hannify, M. Murphy, and H. R. Brady Influence of lipoxin A4 and other lipoxygenase-derived eicosanoids on tissue factor expression Am J Physiol Cell Physiol, October 1, 2000; 279(4): C945 - C953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matetzky, S. Tani, S. Kangavari, P. Dimayuga, J. Yano, H. Xu, K.-Y. Chyu, M. C. Fishbein, P. K. Shah, and B. Cercek Smoking Increases Tissue Factor Expression in Atherosclerotic Plaques : Implications for Plaque Thrombogenicity Circulation, August 8, 2000; 102(6): 602 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krikun, F. Schatz, N. Mackman, S. Guller, R. Demopoulos, and C. J. Lockwood Regulation of Tissue Factor Gene Expression In Human Endometrium by Transcription Factors Sp1 and Sp3 Mol. Endocrinol., March 1, 2000; 14(3): 393 - 400. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Schatz, C. Soderland, K. D. Hendricks-Muñoz, R. P. Gerrets, and C. J. Lockwood Human Endometrial Endothelial Cells: Isolation, Characterization, and Inflammatory-Mediated Expression of Tissue Factor and Type 1 Plasminogen Activator Inhibitor Biol Reprod, March 1, 2000; 62(3): 691 - 697. [Abstract] [Full Text]
|
|
|
|
|
|
M.-Z. Cui, M. S. Penn, and G. M. Chisolm Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1 J. Biol. Chem., November 12, 1999; 274(46): 32795 - 32802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Silverman, C. R. Waters, G. T. Hayman, J. Wigboldus, M. M. Samet, and P. I. Lelkes Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure Am J Physiol Cell Physiol, August 1, 1999; 277(2): C233 - C242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Holzmuller, T. Moll, R. Hofer-Warbinek, D. Mechtcheriakova, B. R. Binder, and E. Hofer A Transcriptional Repressor of the Tissue Factor Gene in Endothelial Cells Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1804 - 1811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Camera, P. L. A. Giesen, J. Fallon, B. M. Aufiero, M. Taubman, E. Tremoli, and Y. Nemerson Cooperation Between VEGF and TNF-{alpha} Is Necessary for Exposure of Active Tissue Factor on the Surface of Human Endothelial Cells Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 531 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Houston, M. C. Dickson, V. Ludbrook, B. White, J.-L. Schwachtgen, J. H. McVey, N. Mackman, J. M. Reese, D. G. Gorman, C. Campbell, et al. Fluid Shear Stress Induction of the Tissue Factor Promoter In Vitro and In Vivo Is Mediated by Egr-1 Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 281 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. R. Pendurthi, J. T. Williams, and L. V. M. Rao Resveratrol, a Polyphenolic Compound Found in Wine, Inhibits Tissue Factor Expression in Vascular Cells : A Possible Mechanism for the Cardiovascular Benefits Associated With Moderate Consumption of Wine Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Hall, H. L. Vos, and R. M. Bertina Lipopolysaccharide Induction of Tissue Factor in THP-1 Cells Involves Jun Protein Phosphorylation and Nuclear Factor kappa B Nuclear Translocation J. Biol. Chem., January 1, 1999; 274(1): 376 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. N. Parry, T. Martin, K. A. Felts, and R. R. Cobb IL-1ß–Induced Monocyte Chemoattractant Protein-1 Gene Expression in Endothelial Cells Is Blocked by Proteasome Inhibitors Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 934 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-J. Shi, P. J. Simpson-Haidaris, N. B. Lerner, V. J. Marder, D. J. Silverman, and L. A. Sporn Transcriptional Regulation of Endothelial Cell Tissue Factor Expression during Rickettsia rickettsii Infection: Involvement of the Transcription Factor NF-kappa B Infect. Immun., March 1, 1998; 66(3): 1070 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krikun, F. Schatz, N. Mackman, S. Guller, and C. J. Lockwood Transcriptional Regulation of the Tissue Factor Gene by Progestins in Human Endometrial Stromal Cells J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 926 - 930. [Abstract] [Full Text]
|
|
|
|
|
|
U. R. Pendurthi, J. T. Williams, and L. V. M. Rao Inhibition of Tissue Factor Gene Activation in Cultured Endothelial Cells by Curcumin : Suppression of Activation of Transcription Factors Egr-1, AP-1, and NF-{kappa}B Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3406 - 3413. [Abstract] [Full Text]
|
|
|
|
|
|
A. D. Schecter, B. J. Rollins, Y. J. Zhang, I. F. Charo, J. T. Fallon, M. Rossikhina, P. L. A. Giesen, Y. Nemerson, and M. B. Taubman Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells J. Biol. Chem., November 7, 1997; 272(45): 28568 - 28573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bierhaus, T. Illmer, M. Kasper, T. Luther, P. Quehenberger, H. Tritschler, P. Wahl, R. Ziegler, M. Muller, and P. P. Nawroth Advanced Glycation End Product (AGE)–Mediated Induction of Tissue Factor in Cultured Endothelial Cells Is Dependent on RAGE Circulation, October 7, 1997; 96(7): 2262 - 2271. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. IMOKAWA, A. SATO, H. HAYAKAWA, M. KOTANI, T. URANO, and A. TAKADA Tissue Factor Expression and Fibrin Deposition in the Lungs of Patients with Idiopathic Pulmonary Fibrosis and Systemic Sclerosis Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 631 - 636. [Abstract] [Full Text]
|
|
|
|
|
|
P. Oeth, G. C.N. Parry, and N. Mackman Regulation of the Tissue Factor Gene in Human Monocytic Cells: Role of AP-1, NF-{kappa}B/Rel, and Sp1 Proteins in Uninduced and Lipopolysaccharide-Induced Expression Arterioscler Thromb Vasc Biol, February 1, 1997; 17(2): 365 - 374. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. M. Boyle Jr, E. D. Verrier, and B. D. Spiess Endothelial Cell Injury in Cardiovascular Surgery: The Procoagulant Response Ann. Thorac. Surg., November 1, 1996; 62(5): 1549 - 1557. [Abstract] [Full Text]
|
|
|
|
|
|
V. Ollivier, G. C.N. Parry, R. R. Cobb, D. d. Prost, and N. Mackman Elevated Cyclic AMP Inhibits NF-kappa B-mediated Transcription in Human Monocytic Cells and Endothelial Cells J. Biol. Chem., August 23, 1996; 271(34): 20828 - 20835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Groupp and M. Donovan-Peluso Lipopolysaccharide Induction of THP-1 Cells Activates Binding of c-Jun, Ets, and Egr-1 to the Tissue Factor Promoter J. Biol. Chem., May 24, 1996; 271(21): 12423 - 12430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Kiely, M. I. Cybulsky, F. W. Luscinskas, and M. A. Gimbrone Jr Immunoselective Targeting of an Anti-Thrombin Agent to the Surface of Cytokine-Activated Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1211 - 1218. [Abstract] [Full Text]
|
|
|
|
|
|
S. Blum, K. Issbruker, A. Willuweit, S. Hehlgans, M. Lucerna, D. Mechtcheriakova, K. Walsh, D. von der Ahe, E. Hofer, and M. Clauss An Inhibitory Role of the Phosphatidylinositol 3-Kinase-signaling Pathway in Vascular Endothelial Growth Factor-induced Tissue Factor Expression J. Biol. Chem., August 31, 2001; 276(36): 33428 - 33434. [Abstract] [Full Text] [PDF]
|
|