15 deoxy delta12,14 PGJ2 induces procoagulant activity in cultured human endothelial cells.
15 deoxy delta12,14 PGJ2 (15d-PGJ2), a high affinity ligand of peroxisome proliferator-activated receptor gamma (PPARgamma) 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-alpha, the subsequent elevation of TF activity was synergistically increased over that of cells treated with TNF-alpha alone and the decline of TF activity after 24 h was less marked than TNF-alpha alone. The induction of TF by 15d-PGJ2 alone and in combination with TNF-alpha was reduced in the presence of PD 98059, suggesting the participation of the MEK/ERK pathway. The thiazolidinedione PPARgamma 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-alpha suggests a pro-inflammatory role for the prostaglandin.
Xie
Shaoping
S
Thrombosis Research Institute, London, UK.
O'Regan
David J
DJ
Kakkar
Vijay V
VV
Scully
Michael F
MF
D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D010641:Phenotype; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D018180:Thrombomodulin / Q000187:drug effects; D019851:Thrombophilia / Q000139:chemically induced* / Q000473:pathology; D013925:Thromboplastin / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014470:Umbilical Cord
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D018836:Inflammation Mediators; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D015230:Prostaglandin D2