Document Detail


The effect of cyclosporin on cell division and apoptosis in human oral keratinocytes.
MedLine Citation:
PMID:  16827723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: Gingival overgrowth (GO) is a side-effect of cyclosporin A (CsA) therapy and is characterised by enlargement of the gingiva with epithelial thickening and overproduction of extracellular matrix components. The pathogenesis of the epithelial thickening in GO remains obscure. The objective of the present study was to investigate the effects of CsA on the growth of oral epithelial cells in vitro and to test the hypothesis that CsA influences apoptosis in these cells. MATERIAL AND METHODS: Cyclosporin was cocultured with an immortalized normal human oral keratinocyte cell line (HOK-16B), an epitheloid cervical carcinoma cell line (HeLa) and primary oral keratinocytes. Cell division was quantified using a CyQUANT kit. Apoptosis was induced using tumour necrosis factor-alpha (TNF-alpha) and assayed by analysis of caspase-3 activity. Expression of the anti-apoptotic protein, Bcl-2, was measured by western blotting. RESULTS: CsA exhibited a dose- and time-dependent inhibition of cell division in all three keratinocyte cell cultures. Significantly, HOK-16B cells treated with high doses of CsA (10 alphag/ml) did not recover their proliferative capacity 3 d after withdrawal of CsA, indicating that CsA-induced inhibition of growth is not temporary. Concentrations of CsA that inhibited cell division (1 microg/ml) did not have any effect on constitutive or TNF-alpha -induced apoptosis or Bcl-2 expression in HOK-16B cells. CONCLUSION: CsA inhibits oral epithelial cell division and this effect is not associated with changes in apoptosis in these cells. The action of CsA on oral epithelial cells may be associated with a long-lasting stress signal, which might account for some of the pathological effects of this drug.
Authors:
J Birraux; J A Kirby; J M Thomason; J J Taylor
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of periodontal research     Volume:  41     ISSN:  0022-3484     ISO Abbreviation:  J. Periodont. Res.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-10     Completed Date:  2006-09-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0055107     Medline TA:  J Periodontal Res     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  297-302     Citation Subset:  D; IM    
Affiliation:
Oral Microbiology and Host Responses Group, School of Dental Sciences, University of Newcastle upon Tyne, UK.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Cell Line, Transformed
Cell Proliferation / drug effects
Cyclosporine / pharmacology*
Gingiva / cytology,  drug effects*,  metabolism
Hela Cells
Humans
Immunosuppressive Agents / pharmacology*
Keratinocytes / drug effects*,  metabolism
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Proto-Oncogene Proteins c-bcl-2; 59865-13-3/Cyclosporine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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