Mechanism of Resveratrol-mediated Suppression of Tissue Factor Gene Expression

SummaryTissue factor (TF) is a cell surface receptor for factor VII(a), and the binding of factor VII(a) to TF initiates the coagulation cascade. Inappropriate in vivo expression of TF in vascular cells has been shown to be responsible for thrombotic disorders associated with a variety of pathological conditions, including gram-negative sepsis, cancer and atherosclerosis. A number of epidemiological studies suggest that moderate consumption of red wine provides protective effects against coronary heart disease mortality. Recently, we have shown that resveratrol, a polyphenolic compound found in wine, inhibited the induction of TF expression in endothelial cells and mononuclear cells (Pendurthi UR, Williams JT, Rao LVM. Arterioscler Thromb Vasc Biol 1999; 19: 419-426). In the present study, we examined the mechanism by which resveratrol inhibits the expression of TF in monocytes by using a monocytic cell line, THP-1, as a model cell. Northern blot analysis, gel mobility shift assays and transfection studies with various TF promoter constructs, as well as other transcription regulatory constructs, were used to elucidate the inhibitory mechanism of resveratrol. The data show that resveratrol inhibited lipopolysaccharide (LPS)-induced expression of TF in human monocytes and monocytic cell line, THP-1 in a dose dependent manner. Resveratrol did not significantly alter the binding of various transcription factors involved in TF gene expression to DNA. However, resveratrol suppressed the transcription of cloned human TF promoter. Further experiments revealed that resveratrol reduced κB- but not AP-1-driven transcriptional activity. Additional experiments showed that resveratrol suppressed the phosphorylation of p65 and its transactivation. In summary, our results indicate that resveratrol does not inhibit the activation or translocation of NF-κB/Rel proteins but inhibits NF-κB/Rel-dependent transcription by impairing the transactivation potential of p65.

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Opposing roles of activator protein-1 and CCAAT/enhancer binding protein beta in the regulation of inducible granulysin gene expression in a human monocytic cell line, THP-1

Immunology ◽

10.1046/j.1365-2567.2002.01524.x ◽

2002 ◽

Vol 107 (4) ◽

pp. 507-516 ◽

Cited By ~ 8

Author(s):

Yutaka Kida ◽

Takashi Shimizu ◽

Koichi Kuwano

Keyword(s):

Gene Expression ◽

Cell Line ◽

Binding Protein ◽

Activator Protein 1 ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Activator Protein ◽

Human Monocytic Cell Line ◽

Enhancer Binding Protein ◽

Human Monocytic Cell

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The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Cells ◽

10.3390/cells8050444 ◽

2019 ◽

Vol 8 (5) ◽

pp. 444 ◽

Cited By ~ 10

Author(s):

Sangiliyandi Gurunathan ◽

Muniyandi Jeyaraj ◽

Min-Hee Kang ◽

Jin-Hoi Kim

Keyword(s):

Cell Line ◽

Chemical Properties ◽

Dependent Manner ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Human Monocytic Cell Line ◽

Physico Chemical ◽

Proinflammatory Responses ◽

Human Monocytic Cell ◽

Dose Dependent

Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.

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Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line

Journal of General Virology ◽

10.1099/0022-1317-73-2-433 ◽

1992 ◽

Vol 73 (2) ◽

pp. 433-435 ◽

Cited By ~ 60

Author(s):

J. H. Sinclair ◽

J. Baillie ◽

L. A. Bryant ◽

J. A. Taylor-Wiedeman ◽

J. G. P. Sissons

Keyword(s):

Gene Expression ◽

Cell Line ◽

Human Cytomegalovirus ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Early Gene Expression

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In vitro effects of monophthalates on cytokine expression in the monocytic cell line THP-1 and in peripheral blood mononuclear cells from allergic and non-allergic donors

Toxicology in Vitro ◽

10.1016/s0887-2333(02)00082-6 ◽

2002 ◽

Vol 16 (6) ◽

pp. 657-662 ◽

Cited By ~ 18

Author(s):

C Glue ◽

A Millner ◽

U Bodtger ◽

T Jinquan ◽

L.K Poulsen

Keyword(s):

Cell Line ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

In Vitro Effects

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Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages

PPAR Research ◽

10.1155/2016/2756781 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

G. Chinetti-Gbaguidi ◽

C. Copin ◽

B. Derudas ◽

N. Marx ◽

J. Eechkoute ◽

...

Keyword(s):

Tissue Factor ◽

Tissue Factor Pathway Inhibitor ◽

Mononuclear Cells ◽

Coagulation Cascade ◽

Factor Vii ◽

Peroxisome Proliferator ◽

Peripheral Blood Mononuclear ◽

Peroxisome Proliferator Activated Receptor ◽

Human Macrophages ◽

Tissue Factor Pathway

Tissue factor (TF) is the initiator of the blood coagulation cascade after interaction with the activated factor VII (FVIIa). Moreover, the TF/FVIIa complex also activates intracellular signalling pathways leading to the production of inflammatory cytokines. The TF/FVIIa complex is inhibited by the tissue factor pathway inhibitor-1 (TFPI-1). Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that, together with PPARα and PPARβ/δ, controls macrophage functions. However, whether PPARγ activation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγ activation increases the expression of TFPI-1 in human macrophages in vitro as well as in vivo in circulating peripheral blood mononuclear cells. The induction of TFPI-1 expression by PPARγ ligands, an effect shared by the activation of PPARα and PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγ ligands significantly reduces the inflammatory response induced by FVIIa, as measured by variations in the IL-8, MMP-2, and MCP-1 expression. These data identify a novel role for PPARγ in the control of TF the pathway.

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