Cyclosporin-induced gingival overgrowth is associated with elevated gene expression for MMP-1, MMP-10 and TIMP-1

Aims: In humans, it has been shown that treatment with theimmunosupressant drug cyclosporin A (CsA) leads to increasedlevels of fibrillar extracellular matrix (ECM) type-1 collagen in theconnective tissue of CsA-induced gingival overgrowth (GO). CsAalso up-regulates gene expression of type-III collagen andproteoglycans (PG). In this context it still remains unclearwhether this increase is associated with alter-ations of moleculesinvolved in the turnover of collagens and PG. Material and methods: The present study explores the status ofMMP-1 and -10 and their tissue inhibitor TIMP-1 on the geneexpression as well as on the protein level on frozen sections derivedfrom GO and normal tissue. Results: In situ hybridization (ISH) revealed elevated levels ofMMP-1 gene expression in the epithelial compartment of GOcompared with normal tissue. This elevation also applied to MMP-10, while MMP-10 gene transcription appeared generally stronger,rather than that observed for MMP-1. For TIMP-1, transcriptionlevels were week in normal and strong in GO tissue. Thesedifferences detected in ISH were corroborated by quantitativeRT-PCR. Detection of the protein by indirect immunofluorescenceshowed that normal gingival tissue was devoid of all three proteins,while they were detectable in GO tissue, with emphasis on TIMP-1. Conclusions: Analysis of our data indicates that in addition toMMP-1 and-10, particularly TIMP-1 may contribute to thepathogenesis of CsA-induced GO. Parole chiave: gingival overgrowth, cyclosporin, matrix-metalloproteinases, gene expression, gingival connective tissue