Fenofibrate inhibits tumor necrosis factor-alpha-induced expression of CD40 and matrix metalloproteinase in human vascular endothelial cells.
OBJECTIVE
To investigate the regulatory effects of fenofibrate on TNF-alpha-induced CD40 expression and matrix metalloproteinase (MMP) activity in human vascular endothelial cells (HUVECs).


METHODS
Quantitative 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.


RESULTS
Fenofibrate 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.


CONCLUSIONS
Fenofibrate reduces TNF-alpha-induced increment of CD40 expression and MMP-2 and MMP-9 activities in HUVECs.
Lin
Rong
R
Department of Pharmacology, Xi'an Jiaotong University, Xi'an 710061, China. linrong@mail.xjtu.edu.cn
Liu
Jun-tian
JT
Gan
Wei-jie
WJ
Wang
Wei-rong
WR
Han
Chun-jie
CJ
Liu
Yu
Y
Fang
Zhi-yuan
ZY
D019013:CD40 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D019013:CD40 Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011345:Fenofibrate