Ox-LDL plays dual effect in modulating expression of inflammatory molecules through LOX-1 pathway in human umbilical vein endothelial cells.
Lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) has been recognized to be the major endothelial receptor for oxidized low-density lipoprotein (ox-LDL). Ox-LDL has been reported to induce the expression of inflammatory adhesive molecules from vascular endothelium. However, the mechanism of this action has not been fully elucidated. Peroxisome proliferation-activated receptor-gamma (PPARgamma) regulates the expression of inflammatory adhesive molecules. The present study was carried out to investigate the role of LOX-1-PPARgamma pathway in regulating expression of adhesion molecules, ICAM-1 and E-selectin in HUVECs. Ox-LDL increased the expression of ICAM-1 and E-selectin in a concentration (10-50 microg/ml)--and time (6-36 hours)--dependent manners. These effects were significantly inhibited by pretreatment of HUVECs with polyinosonic acid or carrageenan. Preincubating HUVECs with 15d-PGJ2 attenuated the expression of ICAM-1 and E-selectin in response to ox-LDL, although ox-LDL stimulated the expression of PPARgamma. Upregulation of ICAM-1 and E-selectin mediated by ox-LDL were inhibited more significantly by the combination of 15d-PGJ2 and polyinosonic acid as compared to either 15d-PGJ2 or polyinosonic acid alone. The results suggested that ox-LDL through its receptor LOX-1 promotes pro-inflammation response by increasing expression of ICAM-1 and E-selectin, simultaneously activates PPARgamma triggering cellular anti-inflammation response in protection from the inflammation lesions in HUVECs.
Zhu
Huilian
H
School of Public Health, Sun-yat-sen University, 74th Zhongshan Road 2, Guangdong, Guangzhou, 510080, PR China.
Xia
Min
M
Hou
Mengjun
M
Tang
Zhihong
Z
Li
Yan
Y
Ma
Jing
J
Ling
Wenhua
W
D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology*
D019040:E-Selectin; D008077:Lipoproteins, LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1