Cyclosporin A inhibits production and activity of matrix metalloproteinases by gingival fibroblasts

Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantat ion and in the management of various autoimmune diseases. Gingival overgrow th is one of the side-effects of the CyA-treatment, affecting the attached gingiva of 25-81% of treated patients. To investigate the production and ac tivity of matrix metalloproteinases (MMPs) in the CyA-induced gingival over growth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts tre ated with CyA. Our results obtained from the Western blot assays demonstrat ed clearly that the production of MMP-1 and MMP-3 was significantly inhibit ed by CyA at similar concentrations found in the serum of patients undergoi ng CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also re duced both in cultured fibroblasts and in the rat CyA-induced gingival over growth. Taken together, the data presented here suggest that these inhibito ry effects may contribute to the extracellular matrix (ECM) components accu mulation in the CyA-induced gingival overgrowth.