[The effect of TLR4/NF-kappaB activation and LOX-1 on monocyte adhesion to endothelium].
OBJECTIVE
Recent studies have shown that Toll-like receptor 4 (TLR4), a mediator of for innate immune responses, is involved in the initiation and progression of atherosclerosis. TLR4 activation mediates the expression of chemokines and cytokines through activation of NF-kappaB. We investigated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (CAM-1), E-selectin induced by TLR4/NF-kappaB in human umbilical vein endothelial cells (HUVECs), and their effects on adhesion of monocyte to HUVECs.


METHODS
HUVECs were incubated with purified LPS for 24 h. TLR4, LOX-1, ICAM-1, E-selectin mRNA were measured by RT-PCR; the protein expression of TLR4, LOX-1 and activation of NF-kappaB were detected by Western blot; the adhesive percentage between HUVECs and monocytes was determined by direct counting.


RESULTS
LPS (1 mg/L) not only enhanced expression of TLR4, activation of NF-kappaB and induction of LOX-1, ICAM-1, E-selectin expression, but also increased the percentage of monocyte adhesion to endothelium. Pretreatment of HUVECs with anti-LOX1, anti-ICAM-1 or anti E-selectin antibodies partly abolished the increase in monocyte adhesion to endothelium. NF-kappaB inhibitor CAPE suppressed LPS-induced these effects.


CONCLUSIONS
TLR4/NF-kappaB plays an important role in monocyte-endothelium adhesion partly through upregulation of LOX-1, ICAM-1 and E-selection expression, which may provide a target for the treatment of atherosclerosis.
Wang
Hong-yan
HY
Department of Cardiology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
Qu
Peng
P
Lu
Shen
S
Liu
Min
M
Jiang
Hua
H
D002448:Cell Adhesion; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D019040:E-Selectin; D016328:NF-kappa B; C495137:OLR1 protein, human; C546936:SELE protein, human; D051127:Scavenger Receptors, Class E; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1