Altered oxidative status and integrin expression in cyclosporine A-treated oral epithelial cells

Background and objective: Cyclosporine A (CsA) is an immunosuppressive agent administered to transplant patients. A well-known reported oral side effect of CsA consumption is gingival overgrowth (GO). Changes in the expression of integrins occurring in the gingiva following CsA treatment have been reported but these reports are mainly concerned with the connective tissue of the gingiva. In this study we targeted the alterations in the oral epithelium using KB cells, an oral epithelial cell line. Methods: Cultured oral epithelial cells were treated with increasing concentrations of CsA (0.1, 1 and 10 mu g/mL) and the molecular changes involving antioxidant enzymes [glutathione peroxidase (GPx) and glutathione reductase (GR)] and the level of reactive oxygen species (ROS) were measured. Quantitative real-time PCR was used to assess the expression of selected integrins (alpha(2), alpha(5) and beta(1)). Results: At CsA concentration above 0.1 mu g/mL GPx demonstrated an increase in activity while GR activity and the level of reduced glutathione were diminished (p<0.05). alpha(5) and beta(1) integrin were downregulated at all treatment concentrations of CsA while alpha(2) integrin presented this effect at concentrations above 1 mu g/mL (p<0.05). Conclusion: The results suggest a possible role for oxidative stress and the altered expression of integrins in the pathology of CsA-induced gingival overgrowth.