Related Experiment Videos
Differences in reactivity to cyclosporin A and interferon-gamma of normal and HPV-transformed keratinocytes
A V Marionnet1, G Lizard, M C Chignol
1INSERM U346 Pavillon, R, Hôpital E. Herriot, Lyon, France.
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.
Insights
Cyclosporin A (CsA) and Interferon-gamma (IFN-gamma) inhibit epithelial cell growth and alter cell cycles, particularly in human papillomavirus (HPV)-transformed cells. These drugs affect normal and HPV-transformed cells differently.
Area of Science:
- Immunopharmacology
- Dermatology
- Oncology
Background:
- Cyclosporin A (CsA) prevents organ transplant rejection but can lead to skin cancers, some linked to human papillomavirus (HPV).
- Interferon-gamma (IFN-gamma) is a local treatment for persistent lesions in the general population.
- The effects of CsA and IFN-gamma on keratinocytes are not fully understood.
Purpose of the Study:
- To investigate the in vitro effects of CsA and IFN-gamma on normal and HPV-transformed epithelial cells.
- To compare the cellular responses to these drugs in different cell types.
Main Methods:
- Normal and HPV-transformed epithelial cell cultures were exposed to varying concentrations of CsA and IFN-gamma for 1-3 days.
- Cell proliferation, morphology, and cell cycle distribution were analyzed.
Main Results:
- No cytotoxicity was observed at the tested concentrations.
- Both CsA and IFN-gamma inhibited cell growth and altered cell morphology.
- CsA induced cytoplasmic vacuoles in some cells.
- Cell cycle analysis revealed S-phase accumulation, especially in HPV-transformed cells, after treatment with higher doses of CsA or IFN-gamma.
Conclusions:
- CsA and IFN-gamma differentially impact normal and HPV-transformed epithelial cells.
- The drugs inhibit cell proliferation and affect cell cycle progression.
- Further research is needed to clarify the specific mechanisms and implications for skin carcinogenesis.