Effect of cyclosporin A on apoptosis of mouse gingival keratinocytes

Objectives: The purpose of the present study was to assess the effect of cyclosporin A(CsA), an potent immunosuppressive drug, on the apoptosis of the keratinocytes of different parts in murine gingival epithelium to investigate the possible mechanism of CsA-induced gingival epithelial hyperplasia . Methods: 50 male ICR mice received CsA dissolved in olive oil (30mgCsA/kg body weight) daily by gastric feeding and contol group took only olive oil. 5 animals from each group were chosen randomly to sacrifice after 1, 2, 4, 6 and 8 wk, respectively.Longitudinal-sections of interdental papilla between mandibular central incisors were used to determine the gingival epithelium thicknesses of different parts including sulcular epithelium(SE), oral sulcular epithelium(OSE) and oral epithelium(OE) by histometry. The longitudinal-sections were also used to detect the apoptosis of keratinocytes in the gingival epithelium by in situ TUNEL assay. The apoptotic rate was determined by the formula in OSE and OE. Results: The epithelial thickness of OSE was obviously thicker in CsA group at all observation time except for 1wk, especially after 4wk(P<0.01) while that in CsA-treated OE showed hardly increase compared to the control group at any time.TUNEL-positive cells were mainly seen in the superficial layers in CsA-group, whereas in the inner were also seen in the contol. After 1 and 2wk, the apoptotic rates of keratinocytes in OSE were significantly decreased in CsA-group (P<0.01)while there were no statistical differences between the two groups after 4 and 6wk(P>0.05) as well as OE at any observation time.Conclusions:CsA can inhibit the apoptosis of keratinocytes in OSE at early time. Thus it indicates that CsA can inhibit apoptosis of epithelial cell before the gingival epithelial hyperplasia occur. The mechanism of CsA-induced gingival epithelial hyperplasia may be associated with CsA inhibition of apoptosis of keratinocytes especially in OSE.