Cyclosporine Effect on MMPs/ TIMPs in Human Gingival Fibroblasts

Introduction: Cyclosporine induced gingival overgrowth has an unknown etiology. Drug-induced gingival overgrowth (DIGO) has become a serious matter recently as the prescription of Cyclosporine increases every year. The aim of this study was to determine whether ECM homeostasis can be affected by MMPs/TIMPS while taking the effect of CsA in adult Human Gingival Fibroblast (HGFs). Methods: Fibroblasts were taken from a cell bank (adult-female), then cultured in PBS, trypsinized and treated with 0, 50, 100 and 150 ng/ml of CsA. Only cells between the third and seventh passage were used. Supernatants were extracted and measured for determining MMPs and TIMPs concentrations in every well. Elisa kits from Boster, CA, USA were used. T-test/ Mann-Whitney was used for statistical analysis. Results : MMP-2 level increased (P<0.05) when compared to the control group. TIMP-2 level also showed significant increment (P<0.05). MMP-1 level increased as dosages of CsA treatment increased from 0 to 50 and 150 ng/ml (P<0.05). TIMP-1 level decreased (P<0.05). Conclusion : MMP-1 (Increase)/TIMP-1 (Decrease) ratio shows the possible effect of CsA on ECM homeostasis. TIMP-2 and MMP-2 both showed more activity while in effect of CsA. This can be attributed to the nature of CsA-induced gingival overgrowth as it is not fibrotic, but it has to be studied more as ratio of MMP-2/TIMP-2 matters. To put the issue into perspective, MMPs and TIMPs can be the possible key solution to the aforementioned vague etiology. Further studies are needed to confirm this hypothesis.