title: Altered oxidative status and integrin expression in cyclosporine A-treated oral epithelial cells.
abstract: 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).
  
  
  CONCLUSIONS
  The results suggest a possible role for oxidative stress and the altered expression of integrins in the pathology of CsA-induced gingival overgrowth.
authors.affiliation: Department of Orthodontics, Orthodontic Research Center, School of Dentistry, Shiraz University of Medical Sciences , Shiraz , Iran .
authors.forename: Ahmadreza
authors.initials: A
authors.lastname: Sardarian
authors.forename: Azadeh
authors.initials: A
authors.lastname: Andisheh Tadbir
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Zal
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Amini
authors.forename: Aida
authors.initials: A
authors.lastname: Jafarian
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Khademi
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Mostafavi-Pour
mesh_terms: D002460:Cell Line; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D039421:Integrin alpha2 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D039421:Integrin alpha2; D039482:Integrin alpha5; D019012:Integrin beta1; D016023:Integrins; D017382:Reactive Oxygen Species; D016572:Cyclosporine; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione
keywords: Cyclosporine; gingival overgrowth; glutathione; integrin α2; integrin α5; integrin β1; reactive oxygen species