Effects of monocyte chemotactic protein-3 on ICAM-1, VCAM-1, TF, and TFPI expression and apoptosis in human umbilical vein endothelial cells.
- Author:
Jinsong CHEN
1
;
Bo ZHANG
;
Congze PAN
;
Lei REN
;
Yundai CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Caspase 3; metabolism; Cell Adhesion; Cells, Cultured; Chemokine CCL7; pharmacology; Chromones; pharmacology; Human Umbilical Vein Endothelial Cells; cytology; drug effects; metabolism; Humans; Intercellular Adhesion Molecule-1; metabolism; Lipoproteins; metabolism; Lipoproteins, LDL; pharmacology; Morpholines; pharmacology; Phosphatidylinositol 3-Kinases; antagonists & inhibitors; Receptors, CCR2; antagonists & inhibitors; Signal Transduction; Thromboplastin; metabolism; Vascular Cell Adhesion Molecule-1; metabolism
- From: Journal of Southern Medical University 2013;33(1):86-92
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of monocyte chemotactic protein-3 (MCP-3) on the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor (TF, and tissue factor pathway inhibitor (TFPI) and cell apoptosis in human umbilical vein endothelial cells (HUVECs).
METHODSCultured HUVECs were treated with MCP-3 at the optimal concentration determined previously 1 h after treatments with or without MCP-3 antibody (20 ng/ml), PI3K inhibitor, or LY-294002 (5 mmol/ml). The expressions of ICAM-1, VCAM-1, TF and TFPI were analyzed using RT-PCR and Western blot after the treatments. MCP-3 mRNA and protein expressions were detected in HUVECs exposed to 50 µg/ml ox-LDL for 24 h. The cell apoptosis and caspase-3 protein production in HUVECs treated with MCP-3 or with MCP-3 plus CCR2 antagonist for 24 h and 48 h were evaluated by flow cytometry and Western blotting.
RESULTSAt the optimal concentration of 0.3 ng/ml, MCP-3 treatment for 24 h caused significantly increased ICAM-1, VCAM-1, and TF expressions with lowered expression of TFPI in HUVECs (P<0.05), and such effects were significantly inhibited by the application of MCP-3 antibody, PI3K inhibitor, or LY-294002 (P<0.05). Ox-LDL exposure significantly increased the expression of MCP-3 in HUVECs (P<0.05). HUVECs showed a significantly increased apoptosis rate after treatment with MCP-3 or with MCP-3 plus CCR2 antagonist (P<0.05), and the apoptosis rate increased significantly as the treatment time prolonged (P<0.05); caspase-3 protein expression in the cells showed a similar pattern of alterations following the treatments.
CONCLUSIONox-LDL can induce MCP-3 expression in HUVECs. MCP-3 induces apoptosis of HUVECs and significantly affects the cellular function partially through the PI3K signaling pathway.
