The immunosuppressant and hyperplasia-inducing drug cyclosporin A regulates the cell cycle and cyclin B1 gene expression in gingival fibroblasts in vitro.
Gingival overgrowth is a frequent and adverse side-effect caused by certain immunosuppressant, anti-convulsant and calcium channel-blocking drugs. Although the precise mechanism is not yet known, the enhanced proliferation of gingival fibroblasts observed in this disease could be caused at least partly by the effects of the drugs on the cell cycle and cyclin expression in these cells. In the present study, flow cytometry analysis of the effects of the immunosuppressant drug cyclosporin A showed that it enhanced cell-cycle progression of gingival fibroblasts in vitro and also up-regulated the expression of cyclin B1. In addition, reverse transcriptase/polymerase chain reaction analysis of gingival overgrowth tissues showed markedly elevated transcription of the cyclin B1 gene. Thus, the increase in cell growth that occurs in drug-induced gingival overgrowth may be mediated by over-expression of cyclin B1.
Parkar
Mohamed H
MH
Periodontology Unit, Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Grays Inn Road, London, UK.
Hussain
Farah
F
Wickramaratna
Ambika
A
Olsen
Irwin
I
D000293:Adolescent; D000328:Adult; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D019926:Cyclin B / Q000096:biosynthesis* / Q000235:genetics; D056744:Cyclin B1; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D005881:Gingiva / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine