Effects of cyclosporine on metalloproteinase in endothelial cells

Cyclosporine (CsA) is a potent agent widely used after organ transplantations and in treatment of various autoimmune disorders. Some patients suffer severe complications including renal and vascular toxicity that are influenced by the degree of endothelial damage. Dysregulation of metalloproteinase (MMP) activity is known to contribute to renal and vascular diseases. To investigate the possible mechanisms of posttransplantation complications in the kidney and vessels by CsA, we examined its effects on metalloproteinases in endothelial cells using human umbilical vein endothelial cells (HUVECs).

HUVECs isolated from umbilical cords by collagenase digestion were seeded in 6-well plates at a density of 1 × 10(5) cells/well before treatment with 2-250 μmol/L CsA and a 24-hour incubation. Thereafter we performed gelatin zymography of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMp-13 to evaluate band density using a luminescent image analyzer system with controls calculated as 100%.

MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 activities were increased after CsA treatment; MMP-1 = 121; MMP-3 = 164; MMP-8 = 133; MMP-9 = 124; and MMP-13 = 121. In contrast, MMP-2 activity was decreased after CsA treatment; MMP-2 = 79.

This study showed CsA to activate most MMPs (except MMP-2) in endothelial cells. This result suggests that CsA may dysregulate MMPs in endothelial cells.