title: Cyclosporine a inhibits apoptosis of rat gingival epithelium.
abstract: BACKGROUND
  The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia.
  
  
  METHODS
  Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels.
  
  
  RESULTS
  In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats.
  
  
  CONCLUSIONS
  CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.
authors.affiliation: Department of Periodontics, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Su
authors.initials: S
authors.lastname: Ma
authors.forename: Peihong
authors.initials: P
authors.lastname: Liu
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D004396:Coloring Agents; D016572:Cyclosporine / Q000494:pharmacology*; D004846:Epithelial Attachment / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D019214:Gingival Overgrowth / Q000139:chemically induced; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004396:Coloring Agents; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016572:Cyclosporine; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Apoptosis; caspase-3; cyclosporine, epithelium; gingival overgrowth; in situ nick-end labeling