The studies described in this proposal are concerned with investigating the interaction of the drug Cyclosporin A with cultured human gingival fibroblasts. Cyclosporin A is a new immunosuppressant that promises to be of great use in the field of transplantation. Unfortunately, basic research on the molecular biology of the drug is very limited. The drugs' target cells are the T-lymphocytes, however, the drug also has an effect on the gingival fibroblasts which manifests itself as the side effect of gingival overgrowth.
The aims of the proposed research are to investigate the drug's effect on cellular proliferation and the G1 phase of cultured gingival fibroblasts, the effect on the phosphorylation of nuclear nonhistone proteins in cultured fibroblasts, and whether these effects can be modulated by the presence of bactorial sonicates. It is known that Phenytoin, the best known inducer of gingival overgrowth, has direct effects on cultured human gingival fibroblasts and similar studies as those proposed herein have been performed by the principal investigator using the drug Phenytoin. As has been the case with Phenytoin, if direct effects of the drug Cyclosporin A can be seen on cultured gingival fibroblasts, more information can be obtained as to the molecular interaction of the drug with human cells. The studies involving the phosphorylated nuclear proteins will be important since the modification of nuclear nonhistone proteins (molecules which are felt to be the regulators of gene transcription) could theoretically be a means by which the drug Cyclosporin A could alter cellular proliferation and cellular functions.
