Mechanism of the Tumor Necrosis Factor α-mediated Induction of Endothelial Tissue Factor

Bierhaus, Angelika; Zhang, Youming; Deng, Youhua; Mackman, Nigel; Quehenberger, Peter; Haase, Michael; Luther, Thomas; Müller, Martin; Böhrer, H.; Greten, Henry Johannes; Martin, Eike; Baeuerle, Patrick A.; Waldherr, Rüdiger; Kisiel, Walter; Ziegler, Reinhard; Stern, David M.; Nawroth, Peter P.

doi:10.1074/jbc.270.44.26419

Cited by 129 publications

(163 citation statements)

References 69 publications

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“…It has been reported that LPS and TNF-␣ induce TF gene expression in monocytic cells and endothelial cells through activation of AP-1 and NF-B transcription factors (9,10,48). Serum stimulates TF gene expression in fibroblasts via AP-1 elements (49), whereas Egr-1 and Sp1 activation principally control TF gene regulation in human epithelial-like HeLa cells in response to serum and phorbol 12-myristate 13-acetate (14).…”

Section: Discussionmentioning

confidence: 99%

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Cui¹,

Penn

Chisolm

1999

Journal of Biological Chemistry

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Tissue factor, in association with factor VIIa, initiates the coagulation cascade. We studied the influences of two pathophysiological stimuli, native (unmodified) and oxidized low density lipoprotein, on tissue factor gene expression in a cell important in vascular remodeling and vascular diseases, the smooth muscle cell. Our results demonstrated that both lipoproteins significantly induced tissue factor gene expression in rat aortic smooth muscle cells; oxidized low density lipoprotein was slightly more potent. Both lipoproteins increased tissue factor mRNA in a concentration-and time-dependent manner. Results from nuclear run-on assays and mRNA stability experiments indicated that increased tissue factor mRNA accumulation in response to the lipoproteins was principally controlled at the transcriptional level. By using lipid extracts of low density lipoprotein or methylation of the intact lipoprotein to block receptor recognition, we showed that this lipoprotein induced tissue factor mRNA via both receptor-independent and receptor-augmented pathways. Transfection studies using a series of deleted tissue factor promoters revealed that a ؊143-to ؉106-base pair region of the rat tissue factor promoter contained regulatory elements required for lipoprotein-mediated induction. Electrophoretic mobility shift assays showed that the binding activities of the transcription factor Egr-1, but not Sp1, were markedly elevated in response to these lipoproteins. Transfection of site-directed mutants of the tissue factor (TF) promoter demonstrated that not only Egr-1 but also Sp1 cis-acting elements in the TF (؊143) promoter construct were necessary for optimal TF gene induction. Our data show for the first time that both low density lipoprotein and oxidized low density lipoprotein induce tissue factor gene expression in smooth muscle cells and that this tissue factor gene expression is mediated by both Egr-1 and Sp1 transcription factors.Tissue factor (TF) 1 expression within the vasculature can activate the coagulation protease cascade and promote thrombotic episodes in a variety of disorders, including cancer, atherosclerosis, and septic shock (reviewed in Refs. 1-3). In atherosclerotic plaques, enhanced TF expression has been detected in association with smooth muscle cells (SMC), macrophages, the lipid-rich necrotic core, and the endothelium overlying the plaque (4 -7). It is important to understand how TF is regulated in SMC, since TF in advancing lesions could exacerbate coagulation after injury, promote SMC proliferation via thrombin generation (8), and reduce atherosclerotic plaque stability.In monocytic cells, endothelial cells, and epithelial cells, TF gene induction by tumor necrosis factor-␣ (TNF-␣), lipopolysaccharide (LPS), phorbol ester (phorbol 12-myristate 13-acetate), and serum is well documented (9 -14). In SMC, serum and various other agonists, including thrombin, platelet-derived growth factor, angiotensin II, and monocyte chemoattractant protein-1, have been shown to induce TF expression in vitro (15,16...

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Section: Discussionmentioning

confidence: 99%

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Cui¹,

Penn

Chisolm

1999

Journal of Biological Chemistry

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“…This suggests that MP may target JNK1 activation in the context of a broad EC stress signaling response, culminating with proinflammatory, proadhesive, and procoagulant gene expression through AP-1 activation. In this context, it is of interest that AP-1 has been implicated in regulated transcription of the TF gene in endothelium (40), and in platelet-derived growth factor-dependent IL-6 gene transcription in osteoblasts (41). Whether this pathway may also influence EC apoptosis (42), thus further exacerbating vessel wall dysfunction and procoagulant activity (43), is cur- FIG.…”

Section: Fig 4 Tf Induction In Mp-stimulated Ecmentioning

confidence: 99%

Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway

Mesri

Altieri

1999

Journal of Biological Chemistry

317

260

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“…After applying the DNA to the cells, cells were cultivated for 1 h before stimulation by AGE-albumin (500 nmol/l) or A␤ (1 mol/l) was performed for 48 h. To correct for efficiency in transfection, we included 0.05 g of pSV-␤-Gal plasmid/ml medium (83). The ratio of luciferase activity to ␤-gal activity served to normalize luciferase activity (83).…”

Section: Diabetes Vol 50 December 2001mentioning

confidence: 99%

“…Tissue culture and transient transfection experiments. BAEC were cultured as previously described (83,87). Bovine arterial smooth muscle cells (SMCs) prepared from bovine aorta were cultured in DMEM containing 10% FCS (88).…”

Section: Diabetes Vol 50 December 2001mentioning

confidence: 99%

Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB

et al. 2001

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Activation of the transcription factor nuclear factor-B (NF-B) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-B in vitro, we observed a long-lasting sustained activation of NF-B in the absence of decreased IB␣ in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-Bp65. A comparable increase in NF-Bp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-␤ peptide ( T issue culture models of cellular activation provide easily accessible systems for detailed analysis of mechanisms potentially underlying the pathogenesis of human disease. However, the time course of such in vitro models is usually significantly abbreviated, limited to hours to days, compared with the pace of disorders under study in vivo. This indicates the importance of seeking out mechanisms in cell culture that might bridge the gap that accounts for the chronicity of cellular perturbation observed in the intact organism.The transcription factor nuclear factor-B (NF-B) has been proposed as a critical bridge between oxidant stress and gene expression (1-8). Exposure of cells to inflammatory, infectious, or other stressful stimuli results in rapid phosphorylation and degradation of IB␣ and the subsequent release and translocation of NF-B into the nucleus (1-11). This mechanism ensures quick and finely tuned cellular responses in the absence of de novo protein synthesis. Because transcription of IB␣ is positively autoregulated by NF-B (9 -11), activation of NF-B is usually self-terminated within minutes to hours (1-11). Such a scenario lends itself to analysis by short-term in vitro studies in which stimulus-induced responses are transient and the system returns to the baseline state over hours. Consequently, induction of NF-B and enhanced transcription of its target genes in vitro have been studied mainly in the setting of acute cellular responses.Reactive oxygen intermediates are generated by processes that occur over seconds. However, increasing evidence suggests a role for oxidative stress in chronic degenerative diseases such as atherosclerosis (1,6,12,13), diabetes (14 -16), and Alzheimer's disease (17)(18)(19). This indicates the relevance of signal transduction systems such as NF-B, which are capable of transforming the appearance and disappearance of short-lived oxygen free radicals into more sustained signals for cellular activation

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Mechanism of the Tumor Necrosis Factor α-mediated Induction of Endothelial Tissue Factor

Cited by 129 publications

References 69 publications

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway

Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB

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