Fenofibrate inhibits tumor necrosis factor-alpha-induced expression of CD40 and matrix metalloproteinase in human vascular endothelial cells.
- Author:
Rong LIN
1
;
Jun-tian LIU
;
Wei-jie GAN
;
Wei-rong WANG
;
Chun-jie HAN
;
Yu LIU
;
Zhi-yuan FANG
Author Information
- Publication Type:Journal Article
- MeSH: CD40 Antigens; biosynthesis; genetics; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; cytology; drug effects; metabolism; Fenofibrate; pharmacology; Flow Cytometry; Humans; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Matrix Metalloproteinases; metabolism; RNA, Messenger; biosynthesis; genetics; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha; pharmacology; Umbilical Veins; cytology
- From: Journal of Southern Medical University 2006;26(10):1383-1387
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the regulatory effects of fenofibrate on TNF-alpha-induced CD40 expression and matrix metalloproteinase (MMP) activity in human vascular endothelial cells (HUVECs).
METHODSQuantitative RT-PCR and flow cytometry were employed to evaluate the effect of fenofibrate on TNF-alpha-induced CD40 mRNA and cell surface CD40 expression in HUVECs, and gelatin zymography was used to determine the effect of fenofibrate on the gelatinolytic activities of MMP-2 and MMP-9 in TNF-alpha-stimulated HUVECs.
RESULTSFenofibrate at the concentrations of 5x10(-5), 1x10(-4) and 2x10(-4) mol/L significantly reduced TNF-alpha-induced increment of CD40 mRNA and cell surface CD40 expressions (P<0.01), with the maximal inhibition achieved at the concentration of 1x10(-4) mol/L. Fenofibrate at 2x10(-4) mol/L did not further decrease CD40 expression induced by TNF-alpha. Fenofibrate significantly inhibited the stimulatory effect of TNF-alpha on MMP-2 and MMP-9 activities in HUVECs.
CONCLUSIONFenofibrate reduces TNF-alpha-induced increment of CD40 expression and MMP-2 and MMP-9 activities in HUVECs.
