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. CONCLUSION: Fenofibrate reduces TNF-alpha-induced increment of CD40 expression and MMP-2 and MMP-9 activities in HUVECs.
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. CONCLUSION:Fenofibrate reduces TNF-alpha-induced increment of CD40 expression and MMP-2 and MMP-9 activities in HUVECs.