title: Cyclosporin A inhibits production and activity of matrix metalloproteinases by gingival fibroblasts.
abstract: Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Gingival overgrowth 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 activity of matrix metalloproteinases (MMPs) in the CyA-induced gingival overgrowth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts treated with CyA. Our results obtained from the Western blot assays demonstrated clearly that the production of MMP-1 and MMP-3 was significantly inhibited by CyA at similar concentrations found in the serum of patients undergoing CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also reduced both in cultured fibroblasts and in the rat CyA-induced gingival overgrowth. Taken together, the data presented here suggest that these inhibitory effects may contribute to the extracellular matrix (ECM) components accumulation in the CyA-induced gingival overgrowth.
authors.affiliation: Department of Oral Pathology and Genetics, School of Dentistry of Piracicaba, UNICAMP, SP, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Bolzani
authors.forename: R
authors.initials: R
authors.lastname: Della Coletta
authors.forename: H
authors.initials: H
authors.lastname: Martelli Júnior
authors.forename: H
authors.initials: H
authors.lastname: Martelli Júnior
authors.forename: E
authors.initials: E
authors.lastname: Graner
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000201:enzymology; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D016572:Cyclosporine; D020782:Matrix Metalloproteinases