Activated protein C ameliorates TNF-alpha-induced inflammatory response of endothelium via the endothelial protein C receptor.
- Author:
Youqin CHEN
1
;
Jun PENG
;
Xiaoheng LIU
;
Jiang WU
;
Ruheng LI
;
Xiaohong ZHENG
Author Information
1. Department of Pediatrics, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73190, USA. yunnansummer@hotmail.com
- Publication Type:Journal Article
- MeSH:
Antigens, CD;
metabolism;
Cells, Cultured;
Cytokines;
metabolism;
Endothelial Protein C Receptor;
Human Umbilical Vein Endothelial Cells;
drug effects;
Humans;
Inflammation;
metabolism;
Protein C;
pharmacology;
Receptors, Cell Surface;
metabolism;
Tumor Necrosis Factor-alpha;
antagonists & inhibitors
- From:
Journal of Biomedical Engineering
2009;26(3):625-630
- CountryChina
- Language:English
-
Abstract:
It has been demonstrated that the activated protein C (APC) plays an important role in the inhibition of inflammation. The activation of protein C can be significantly enhanced by the endothelial cell protein C receptor (EPCR). Previous studies proposed that the APC regulates the inflammatory response in endothelial cells by suppressing the expression of adhesion molecules and the secretion of chemokines and cytokines. However, the precise mechanism of the inhibitory effect of APC on inflammation is still poorly understood. In the present study, we evaluated the anti-inflammatory effect of recombinant human APC (rhAPC) and whether its inhibitory effect is conducted through the EPCR-dependent mechanism on human umbilical vein endothelial cells (HUVECs). By exposing HUVECs to: (1) TNF-alpha; (2) rhAPC plus TNF-alpha; (3) anti EPCR antibody that prevents rhAPC interaction with EPCR; (4) TNF-alpha plus anti EPCR antibody; (5) rhAPC plus TNF-alpha in the presence of anti EPCR antibody, we found that APC was able to significantly inhibit the TNF-alpha-induced secretion of cytokines such as IL-1beta and IL-8, as well as the expression of adhesion molecules such as ICAM-1, VCAM-1 and E-selction in HUVECs. These results reveal a novel pathway by which APC protects endothelial cells from inflammatory mediators through an EPCR-dependent mechanism.
