Efeitos da ciclosporina-A na produção e atividade de metaloproteinases de matriz por fibroblastos gengivais

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

Cyclosporin A (CyA) is an immunossupressant drug used to prevent rejection of allograft transplants and in the management of various autoimmune diseases that acts blocking interleukin-2 synthesis by CD4+lymphocytes. The gingival overgrowth affecting the attached gingiva of 25-80% of the treated patients, is a frequent side effect of CyA treatment in the oral cavity. The aim of the present work was to evaluate the effect of CyA on matrix metalloproteinases (MMPs) synthesis and activity as well as type I collagen production by gingival fibroblasts. Wistar rats were treated daily with 10mg/kg of body weight of CyA during 30 and 60 days to induce gingival overgrowth. After these periods, the gingival tissue was removed and used to study MMPs activity in zymographic assays as well as type I collagen deposition by SDS-PAGE. Primary cultures of fibroblasts from rats and 7 different clinically healthy human gingiva were established and used to analyze secretion and activity of MMPs in the culture medium. The cells were treated with different concentrations of CyA and analised by zymographic assays and western blots. The gelatinolytic activity of MMP-2 was strongly reduced by CyA treatment, both "in vivo" and in cell culture. In addition, the relative amounts of MMP-1 and MMP-3 in the culture medium was significanty reduced by CyA treatment and the amount of type I collagen in the hyperplastic rat gingival tissue was higher than in control animais. Our data clearly showed that CyA strongly reduces the activity and production of MMPs by gingival fibroblasts, probably leading to the accumulation of type I collagen and other macromolecules in the gingival connective tissue

ASSUNTO(S)

hiperplasia gengivas ciclosporina proteinase

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