Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2756781 |
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| author | G. Chinetti-Gbaguidi C. Copin B. Derudas N. Marx J. Eechkoute B. Staels |
| author_facet | G. Chinetti-Gbaguidi C. Copin B. Derudas N. Marx J. Eechkoute B. Staels |
| author_sort | G. Chinetti-Gbaguidi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-20f6f2b82c5b45b69d18ed2cd4b622e6 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-20f6f2b82c5b45b69d18ed2cd4b622e62025-02-03T05:52:13ZengWileyPPAR Research1687-47571687-47652016-01-01201610.1155/2016/27567812756781Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human MacrophagesG. Chinetti-Gbaguidi0C. Copin1B. Derudas2N. Marx3J. Eechkoute4B. Staels5Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, FranceInserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, FranceInserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, FranceDepartment of Cardiology, RWTH Aachen University, Aachen, GermanyInserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, FranceInserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, FranceTissue 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.http://dx.doi.org/10.1155/2016/2756781 |
| spellingShingle | G. Chinetti-Gbaguidi C. Copin B. Derudas N. Marx J. Eechkoute B. Staels Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages PPAR Research |
| title | Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages |
| title_full | Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages |
| title_fullStr | Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages |
| title_full_unstemmed | Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages |
| title_short | Peroxisome Proliferator-Activated Receptor γ Induces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages |
| title_sort | peroxisome proliferator activated receptor γ induces the expression of tissue factor pathway inhibitor 1 tfpi 1 in human macrophages |
| url | http://dx.doi.org/10.1155/2016/2756781 |
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