title: Differences in reactivity to cyclosporin A and interferon-gamma of normal and HPV-transformed keratinocytes.
abstract: In humans, cyclosporin A (CsA) avoids organ allograft rejection but induces skin carcinomas after long term immunosuppressive treatment; some of these lesions contain human papillomavirus (HPV) DNA. Interferon-gamma (IFN-gamma) is sometimes used in local treatment of persistent or recurrent lesions in normal population. In vivo, both drugs have an effect on keratinocytes which remains unclear. Therefore, their effect was studied on in vitro models of normal or HPV-transformed epithelial cell cultures. After exposure of proliferating cells for 1-3 days to 0.5-16 micrograms/ml CsA and 5-160 U/ml IFN-gamma, no cytotoxicity was observed; cell growth was inhibited; cell morphology was altered with CsA and cytoplasmic vacuoles were seen in some cells. Changes in the cell cycle were mainly obtained after treatment with 8 micrograms/ml CsA or 160 U/ml IFN-gamma, with an accumulation in S-phase especially in HPV-transformed cells. Thus, CsA and IFN-gamma affected, normal and HPV-transformed epithelial cells, differently.
authors.affiliation: INSERM U346 Pavillon, R, Hôpital E. Herriot, Lyon, France.
authors.forename: A V
authors.initials: AV
authors.lastname: Marionnet
authors.forename: G
authors.initials: G
authors.lastname: Lizard
authors.forename: M C
authors.initials: MC
authors.lastname: Chignol
authors.forename: Y
authors.initials: Y
authors.lastname: Chardonnet
authors.forename: D
authors.initials: D
authors.lastname: Schmitt
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D002452:Cell Count / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics*; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D007371:Interferon-gamma; D016572:Cyclosporine; C022616:thiazolyl blue