Thrombin Augments LPS-Induced Human Endometrial Endothelial Cell Inflammation via PAR1 Activation.
Risk factors for preterm birth include placental abruption, giving rise to excessive decidual thrombin, and intrauterine bacterial infection. Human endometrial endothelial cells (HEECs) express Toll-like receptors (TLRs), and infection-derived agonists trigger HEECs to generate specific inflammatory responses. As thrombin, in addition to inducing coagulation, can contribute to inflammation, its effect on HEEC inflammatory responses to the TLR4 agonist, bacterial lipopolysaccharide (LPS), was investigated.



HEECs were pre-treated with or without thrombin or specific protease-activated receptor (PAR) agonists, followed by treatment with or without LPS. Supernatants were measured for cytokines and chemokines by ELISA and multiplex analysis.



Thrombin significantly and synergistically augmented LPS-induced HEEC secretion of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), and growth-regulated oncogene-alpha (GRO-α), and significantly augmented monocyte chemotactic protein (MCP)-1, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) secretion additively. Similar to thrombin, a PAR1 agonist synergistically augmented the LPS-induced HEEC secretion of inflammatory IL-6, IL-8, G-CSF, and GRO-α.



Thrombin, via PAR1 activation, synergistically augments LPS-induced HEEC production of chemokines involved in immune cell recruitment and survival, suggesting a mechanism by which intrauterine abruption and bacterial infection may together be associated with an aggravated uterine inflammatory response.
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Mohak V
MV
Mhatre
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Julie A
JA
Potter
Department of Obstetrics & Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Charles J
CJ
Lockwood
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Graciela
G
Krikun
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Vikki M
VM
Abrahams
D016207:Cytokines / Q000276:immunology; D004717:Endometrium / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D044463:Receptor, PAR-1 / Q000276:immunology*; D013917:Thrombin / Q000276:immunology*
D016207:Cytokines; D008070:Lipopolysaccharides; D044463:Receptor, PAR-1; D013917:Thrombin
Endothelial; infection; inflammation; pregnancy; thrombin