Effect of Immunosuppressive Drugs on the Metalloproteinase in the Glioma Cells and Osteoblasts

Abstract

The matrix metalloproteinases (MMPs) play a key role in the normal physiology of connective tissue during development, morphogenesis, and wound healing. Dysregulation of their activity has been implicated in numerous diseases including encephalopathy and the process of bone loss. Thus, MMPs may play a role in the encephalopathy and post-transplantation bone disease by immunosuppressive drugs such as cyclosporine (CsA) and tacrolimus. Gelatin zymography of MMP-9 and MMP-2 was performed in the glioma cells and osteoblast after CsA or tacrolimus treatment. Glioma cells or rat osteoblast ROS17/2.8 cells were treated with CsA or tacrolimus to make final concentration from 2 to 250 μM. After incubation, gelatin zymography of MMP-9 and MMP-2 was performed. And the density for the MMP bands were measured using luminescent image analyzer system. Both MMP-9 and MMP-2 activities in the osteoblast cells were decreased depending on the concentration of CsA or tacrolimus. MMP-2 activity was increased after CsA or tacrolimus treatment in the glioma cells. However, MMP-9 activities were decreased after CsA or tacrolimus treatment in the glioma cells. These results indicate that dysregulation of MMPs in the osteoblast and in the glioma cells by immunosuppressive drugs may one of the contributing factors in post-transplantation bone disease and in the encephalopathy by tacrolimus or cyclosporine.