title: Cyclosporin-A inhibits the expression of cyclooxygenase-2 in gingiva.
abstract: OBJECTIVE
  Various inflammatory mediators are involved in the development of cyclosporine A-induced gingival overgrowth. In this study, the gingival expression of cyclooxygenase-2 after cyclosporine A therapy was examined in vivo and in vitro.
  
  
  METHODS
  After edentulous ridges on maxilla were established, 21 Sprague-Dawley rats received cyclosporine A daily for 4 wk, and a further 21 rats received solvent. After the rats were killed, the expression of cyclooxygenase-2 mRNA, interleukin-1beta mRNA, tumor necrosis factor-alpha mRNA, and interleukin-6 mRNA was examined in the edentulous gingiva. The expression of cyclooxygenase-2 protein and the production of prostaglandin E2 were also evaluated.
  
  
  RESULTS
  In cultured human gingival fibroblasts and epithelial cells, the expression of cyclooxygenase-2 mRNA was measured after treatment with cyclosporine A. Significantly lower expression of cyclooxygenase-2 and interleukin-1beta mRNA, but higher interleukin-6 expression, were observed in gingiva from cyclosporine A-treated rats than in those from the control rats. Significantly less prostaglandin E2 production was observed in cyclosporine A-treated rats. Immunohistochemistry revealed that fewer gingival stromal cells were positively stained for cyclooxygenase-2 in cyclosporine A-treated rats. In cultured cells, significantly less cyclooxygenase-2 mRNA was detected after treatment with cyclosporine A.
  
  
  CONCLUSIONS
  The expression of cyclooxygenase-2 was lower in the plaque nonretentive gingivae and the in vitro gingival cells upon treatment with cyclosporine A. Thus, we propose that cyclosporine A inhibits the expression of gingival cyclooxygenase-2.
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chiang
authors.forename: Y-T
authors.initials: YT
authors.lastname: Chen
authors.forename: F-M
authors.initials: FM
authors.lastname: Hung
authors.forename: H-P
authors.initials: HP
authors.lastname: Tu
authors.forename: M M-J
authors.initials: MM
authors.lastname: Fu
authors.forename: E
authors.initials: E
authors.lastname: Fu
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007575:Jaw, Edentulous / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D051546:Cyclooxygenase 2; D015232:Dinoprostone