Preliminary Study On Mechanisms Of Cyclosporine A-induced Gingival Overgrowth

Objective: 1. To investigate the relationship between cyclosporine A(CsA) blood concentration of patients who have received renal transplantation and the development of gingival overgrowth. 2 . To observe differences of the cellular proliferation of normal and overgrown gingival fibroblasts cultured under different concentrations of CsA . 3. To detect and compare the expression levels of keratinocyte growth factor( KGF) in normal and overgrown gingival tissues.Methods: 1. To record the CsA blood concentration of 42 patients who have received renal transplantation and the information of gingival overgrowth. 2. The gingival fibroblasts were cultured and counted with various concentrations of cyclosporine A(1200.0μg/L, 360.0μg/L, 108.0μg/L and 32.4μg/L);The DNA synthesis of gingival fibroblasts were surveyed by 3H-thymidine(3H-TdR) incorporated experiment. 3.Three biopsy tissues derived from normal gingiva ,and three biopsy tissues derived from cyclosporine A-induced gingival overgrowth were used to study the KGF expression levels by immuno-histochemical assay. 4.The KGF outputs were determinated by enzyme-linked immunosorbent assay in normal and overgrown gum.Results: 1 .There is a close correlation between CsA blood concentration and gingival overgrowth in 42 renal transplantation patients (x2 =12.51, p<0.001) . 2. The numbers of cultured cells from normal and overgrown fibroblasts increased day by day in one week. No difference was found between different groups of different drug concentrations in first 5 days. On 6th and 7th day, significant differences of cell numbers were found between high dose groups (1200μg/L and 360μg/L) and low dose groups(108μg/L and 32.4μg/L).But there is no difference between normal fibroblasts groups and overgrown fibroblasts groups in all 7 days process. 3. The DNA synthesis determined by 3H-thymidine addition assay in normal fibroblasts corelated with the concentration of CsA .4.The expression of KGF cound be found in the whole connective tissues and the cornified layer of gingival epithelium while little cound be found in the other layers of gingival epithelium of overgrown tissues. On the other hand,the expression of KGF cound not be found in any parts of connective tissues and gingival epithelium layers of normal gingiva tisues. 5.CsA cound stimulate KGF outputs of normal gingival fibroblasts under all 4 drug concentrations used in this study while only the highest drug concentration(2000ng/ml) cound stimulate KGF output in gingival fibroblasts isolated from overgrown tissues. Addition of 1 OOng/ml CsA resulted in a small but still observable inhibition of KGF expression and addition of 500ng/ml CsA cound induced a marked reduction of KGF production in all three overgrown strains of gingival fibroblasts.Conclusions: The occurrence of gingival overgrowth was closely corelated with the blood concentration of cyclosporine A in renal transplantation patients;Cyclosporin A can stimulate the proliferation of gingival fibroblasts at high concentration;KGF may play an important role in cyclosporine A-induced gingival overgrowth.