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The Effects of Cyclosporin on the Collagenolytic Activity of Gingival Fibroblasts
Author(s) -
Hyland Paula L.,
Traynor Patrick S.,
Myrillas Theofilos T.,
Marley John J.,
Linden Gerard J.,
Winter Paul,
Leadbetter Nicola,
Cawston Timothy E.,
Irwin Chris R.
Publication year - 2003
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2003.74.4.437
Subject(s) - matrix metalloproteinase , connective tissue , messenger rna , extracellular matrix , real time polymerase chain reaction , chemistry , reverse transcription polymerase chain reaction , pathogenesis , microbiology and biotechnology , biology , biochemistry , immunology , gene , genetics
Background: The immunosuppressive agent cyclosporin is associated with a number of major side‐effects including the development of gingival overgrowth. Although the pathogenesis of cyclosporin‐induced gingival overgrowth remains unclear, it has been suggested that the finely regulated balance between extracellular matrix synthesis and degradation may be disturbed, resulting in an accumulation of excess connective tissue components within the gingival tissue. The aim of this study was to investigate the effect of cyclosporin on matrix metalloproteinases (MMP)‐1 and tissue inhibitors of MMP (TIMP)‐1 expression at the mRNA, protein, and enzyme activity levels. Methods: Gingival fibroblasts were grown to confluence and then cultured in serum‐free medium supplemented with cyclosporin over the concentration range of 0 to 2000 ng/ml. MMP‐1 and TIMP‐1 mRNA levels in cultures were determined by reverse transcription polymerase chain reaction (RT‐PCR), protein levels in whole conditioned medium were assessed by enzyme‐linked immunosorbent assay (ELISA), and collagenolytic activity determined using a 3 H‐acetylated type I collagen degradation assay. Tissue mRNA levels in normal and overgrown gingiva were also determined by RT‐PCR. Results: Results indicated that cyclosporin inhibited MMP‐1 expression at both the mRNA and protein level in a dose‐ and time‐dependent fashion. The effects on TIMP‐1 expression were less clear, cyclosporin inhibiting mRNA expression, but having no effect on TIMP‐1 protein levels at any concentration studied. Addition of the drug resulted in reduced levels of collagenolytic activity in the culture medium. MMP‐1 mRNA expression was significantly reduced in overgrown compared to normal tissue. Conclusions: These results add support to the hypothesis that the accumulation of collagen seen in gingival overgrowth can be explained by a cyclosporin‐induced inhibition of collagenolytic activity within the gingival tissues. J Periodontol 2003;74:437‐445 .