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

Abstract

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 µg/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 (α₂, α₅ and β₁).

Results: At CsA concentration above 0.1 µg/mL GPx demonstrated an increase in activity while GR activity and the level of reduced glutathione were diminished (p < 0.05). α₅ and β₁ integrin were downregulated at all treatment concentrations of CsA while α₂ integrin presented this effect at concentrations above 1 µg/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.

• Cyclosporine
• gingival overgrowth
• glutathione
• integrin α₂
• integrin α₅
• integrin β₁
• reactive oxygen species

Acknowledgements

The authors would also like to thank the student Research Committee and Orthodontic Research Center for their support in writing this manuscript. Determination of the oxidative status following CsA treatment explained in this study is based on the thesis by Dr Ahmadreza Sardarian.

Declaration of interest

The authors thank the Vice-Chancellery of Shiraz University of Medical Sciences for supporting this research (Grant # 1371). There is no conflict of interest pertaining to any of the authors of the manuscript.