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 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. © 2016 g. chinetti-gbaguidi et al.