Transcriptional regulation of tissue factor expression in human endothelial cells.

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-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), 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 kappa B-like site, that mediated induction by TNF-alpha, IL-1 beta, and LPS. Electrophoretic mobility shift assays demonstrated that endothelial cells contained constitutive AP-1 binding activity, whereas the kappa 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.

[1]  N. Mackman,et al.  A set of inducible genes expressed by activated human monocytic and endothelial cells contain kappa B-like sites that specifically bind c-Rel-p65 heterodimers. , 1994, The Journal of biological chemistry.

[2]  C. Rosen,et al.  Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site , 1994, Molecular and cellular biology.

[3]  N. Mackman,et al.  Regulation of tissue factor gene expression in epithelial cells. Induction by serum and phorbol 12-myristate 13-acetate. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[4]  P. Baeuerle,et al.  Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription , 1994, Molecular and cellular biology.

[5]  J. Johnson,et al.  12-O-tetradecanoylphorbol-13-acetate- and tumor necrosis factor alpha-mediated induction of intercellular adhesion molecule-1 is inhibited by dexamethasone. Functional analysis of the human intercellular adhesion molecular-1 promoter. , 1994, The Journal of biological chemistry.

[6]  Amyj . Williams,et al.  NF-kappa B and I kappa B alpha: an inducible regulatory system in endothelial activation , 1994, The Journal of experimental medicine.

[7]  S. Akira,et al.  Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Baldwin,et al.  Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B , 1993, Molecular and Cellular Biology.

[9]  M. Read,et al.  Cell-free pool of CD14 mediates activation of transcription factor NF-kappa B by lipopolysaccharide in human endothelial cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T. Drake,et al.  Regulation of endothelial cell tissue factor expression by minimally oxidized LDL and lipopolysaccharide. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[11]  W. Greene,et al.  Cross‐coupling of the NF‐kappa B p65 and Fos/Jun transcription factors produces potentiated biological function. , 1993, The EMBO journal.

[12]  H. Samuels,et al.  The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements , 1993, Molecular and cellular biology.

[13]  M. Read,et al.  Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. , 1993, The Journal of biological chemistry.

[14]  T. Drake,et al.  Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. , 1993, The American journal of pathology.

[15]  M. Lenardo,et al.  Interaction between NF-kappa B- and serum response factor-binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes , 1993, Molecular and cellular biology.

[16]  W C Greene,et al.  NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. , 1993, Science.

[17]  N. Fausto.  What's in a Name? The American Society for Investigative Pathology. , 1993, The American journal of pathology.

[18]  M. Grilli,et al.  NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. , 1993, International review of cytology.

[19]  S. Ruben,et al.  I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention. , 1992, Genes & development.

[20]  T. Drake,et al.  Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[21]  S. Ruben,et al.  Functional characterization of the NF-kappa B p65 transcriptional activator and an alternatively spliced derivative , 1992, Molecular and cellular biology.

[22]  N. Mackman,et al.  Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites , 1991, The Journal of experimental medicine.

[23]  N. Mackman,et al.  Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide , 1991, Molecular and cellular biology.

[24]  S. Caughman,et al.  Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene. , 1991, The Journal of biological chemistry.

[25]  N. Mackman,et al.  The Structural Biology of Expression and Function of Tissue Factor , 1991, Thrombosis and Haemostasis.

[26]  F. Taylor,et al.  Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. , 1991, Circulatory shock.

[27]  D. Crossman,et al.  The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester. , 1990, The Journal of biological chemistry.

[28]  T. van der Poll,et al.  Activation of coagulation after administration of tumor necrosis factor to normal subjects. , 1990, The New England journal of medicine.

[29]  S. Rapaport,et al.  Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. , 1990, Blood.

[30]  T. Curran,et al.  Encounters with Fos and Jun on the road to AP-1. , 1990, Seminars in cancer biology.

[31]  J. Sadler,et al.  Regulation of endothelial cell coagulant properties. Modulation of tissue factor, plasminogen activator inhibitors, and thrombomodulin by phorbol 12-myristate 13-acetate and tumor necrosis factor. , 1989, The Journal of biological chemistry.

[32]  K. Matsushima,et al.  Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. , 1989, Journal of immunology.

[33]  R. Tjian,et al.  Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. , 1989, Science.

[34]  T. Edgington,et al.  Monoclonal antibody analysis of purified and cell-associated tissue factor. , 1988, Thrombosis research.

[35]  A. Cerami,et al.  Detection of circulating tumor necrosis factor after endotoxin administration. , 1988, The New England journal of medicine.

[36]  R. Bach.  Initiation of Coagulation by Tissue Facto , 1988 .

[37]  C. Esmon.  The regulation of natural anticoagulant pathways , 1987, Science.

[38]  K. Wood,et al.  Firefly luciferase gene: structure and expression in mammalian cells , 1987, Molecular and cellular biology.

[39]  C. Morency,et al.  A novel rapid assay for chloramphenicol acetyltransferase gene expression , 1987 .

[40]  C. Esmon,et al.  Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. , 1987, The Journal of clinical investigation.

[41]  W. Fiers,et al.  Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[42]  D. Lawrence,et al.  Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. , 1984, The Journal of biological chemistry.

[43]  R. Cotran,et al.  Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells , 1984, The Journal of experimental medicine.

[44]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[45]  N. Semeraro,et al.  Cultured human endothelial cells generate tissue factor in response to endotoxin. , 1983, The Journal of clinical investigation.

[46]  I. Pastan,et al.  The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. , 1982, Proceedings of the National Academy of Sciences of the United States of America.