title: Peroxisome Proliferator-Activated ReceptorγInduces the Expression of Tissue Factor Pathway Inhibitor-1 (TFPI-1) in Human Macrophages.
abstract: 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 PPARαand PPARβ/δ, controls macrophage functions. However, whether PPARγactivation modulates the expression of TFP1-1 in human macrophages is not known. Here we report that PPARγactivation 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 PPARγligands, an effect shared by the activation of PPARαand PPARβ/δ, occurs also in proinflammatory M1 and in anti-inflammatory M2 polarized macrophages. As a functional consequence, treatment with PPARγligands 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 PPARγin the control of TF the pathway.
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, France; CHU, CNRS, Inserm, IRCAN, Université Côte d'Azur, Nice, France.
authors.forename: G
authors.identifier: 0000-0001-8048-8138
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Copin
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, France.
authors.forename: B
authors.initials: B
authors.lastname: Derudas
authors.affiliation: Department of Cardiology, RWTH Aachen University, Aachen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Marx
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, France.
authors.forename: J
authors.identifier: 0000-0002-7222-9264
authors.initials: J
authors.lastname: Eechkoute
authors.affiliation: Inserm, CHU Lille, Institut Pasteur de Lille, U1011, EGID, Université de Lille, 59000 Lille, France.
authors.forename: B
authors.identifier: 0000-0002-3784-1503
authors.initials: B
authors.lastname: Staels