Effects of cyclosporine and phenytoin on biomarker expressions in gingival fibroblasts of children and adults: an in vitro study.

BACKGROUND

Both phenytoin (PhT) and cyclosporine (CsA) have been related to gingival overgrowth, but the presence and incidence of cytokines in gingival tissues are associated with different mechanisms. On the basis of a few epidemiologic data, children are more prone to have gingival overgrowth than adults and there is no obvious plausibility to justify this difference. The aim of this study was to investigate the effect of PhT and CsA on the some biological marker expression and compare it among adults and children.

METHODS

Gingival fibroblasts that had been harvested from adults and children with normal gingiva were incubated with CsA and PhT and then cultured for 48 h. Matrix metalloproteinases (MMP-1 and MMP-2), tissue inhibitor of metalloproteinases (TIMP), collagen (CoL), elastin (Eln), lysyl oxidase (Lysyl), cathepsin (Cat) L and B, and mRNA levels in culture were determined by reverse transcription polymerase chain reaction. The amounts of transforming growth factor-β (TGF-β) and epidermal growth factor (EGF) were assessed by enzyme-linked immunosorbent assay.

RESULTS

CsA and PhT stimulated TGF-β and Cat B production and inhibited expression of MMP-1 by fibroblasts. CsA suppressed TIMP in children, but PhT stimulated its expression. In adults, both CSA and PHT increased TGF-β, Lysyl, and EGF levels. CsA reduced Eln level, whereas PhT increased it.

CONCLUSIONS

The results suggest that CsA and PhT have different effects on biogene marker expression in adults and children, or drug-induced gingival overgrowth is affected by different cellular pathways in children in contrast to that in adults. It seems that in children the MMP-1/TIMP system, and in adults the Lysyl/Eln pathway, plays an important role in impaired CoL metabolism.