Regulation of human gingival fibroblast growth and synthetic activity by cyclosporine-A in vitro.
Gingival overgrowth is an adverse side-effect seen in a proportion of patients taking cyclosporin-A which indicates that cyclosporine-A may modulate the activities of cells other than T lymphocytes. Therefore, the effect of cyclosporine on human gingival fibroblasts has been studied in vitro. Cyclosporine-A was found to stimulate DNA synthesis and the proliferative activity of these cells with maximal stimulation noted at a concentration of 10(-9) g/ml. Although this stimulation was most noticeable in the presence of 10% fetal calf serum, proliferation still occurred in serum-free medium. In the presence of lipopolysaccharide, at a concentration which normally inhibits gingival fibroblast proliferation, cyclosporine retained its capacity to stimulate proliferative activity. Fibroblasts isolated from overgrown gingival tissue responded to a greater extent than those isolated from a healthy site from the same individual. This stimulatory effect was not restricted to gingival fibroblasts, since human foreskin fibroblasts responded in a similar fashion. Cyclosporine-A did not significantly alter protein or proteoglycan production by these cells. These responses are considered to reflect the in vivo response of gingival overgrowth in patients taking cyclosporine-A. The reversal of lipopolysaccharide inhibition of gingival fibroblast proliferation by cyclosporine-A may explain, in part, why gingival overgrowth is most prominent in areas of heavy dental plaque accumulation.
Bartold
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D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D014176:Protein Biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D003524:Cyclosporins; D011509:Proteoglycans; D004247:DNA