15 Deoxy Δ^12,14 PGJ₂ Induces Procoagulant Activity in Cultured Human Endothelial Cells

Summary

15 deoxy Δ^12,14 PGJ₂ (15d-PGJ₂), a high affinity ligand of peroxisome proliferator-activated receptor γ (PPAR γ has been proposed to act as a negative feedback regulator of the inflammatory response. We investigated the effect of 15d-PGJ₂ on the anticoagulant property of endothelial cells. 15d-PGJ₂ stimulated a moderate but sustained increase in tissue factor (TF) activity in HUVECs and EA.hy926 cells while causing a partial loss of thrombomodulin (TM) activity. When cells were co-treated with 15d-PGJ₂ and TNF-α, the subsequent elevation of TF activity was synergistically increased over that of cells treated with TNF-α, alone and the decline of TF activity after 24 h was less marked than TNF-α, alone. The induction of TF by 15d-PGJ₂ alone and in combination with TNF-α, was reduced in the presence of PD 98059, suggesting the participation of the MEK/ERK pathway. The thiazolidinedione PPAR γ agonist ciglitazone had no effect on TF levels but reduced the expression of endothelial protein C receptor. The ability of 15d-PGJ₂ to enhance a procoagulant phenotype arising from TNF-α, suggests a pro-inflammatory role for the prostaglandin.

Keywords

15 deoxy Δ12,14 PGJ₂ - peroxisome proliferator-activated receptor γ - tissue factor - thrombomodulin - endothelial cells

^* Present address: Dr. D. J. O’Regan, Department of Cardiac Surgery, General Infirmary, Leeds, UK

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