Cyclosporin A and hydroxycyclosporine (M-17) affect the secretory phenotype of human gingival fibroblasts.
The responsiveness of human gingival fibroblast populations to cyclosporin A (CsA) and its principal metabolite, hydroxycyclosporine (M17), was evaluated in cell culture. Gingival fibroblasts exhibited a dose-dependent accumulation and bell-shaped distribution of dansylated CsA. A 100-fold excess of non-labeled CsA prevented the accumulation of the fluorescent probe in the fibroblasts. Both CsA (400 ng/ml) and M17 (100 ng/ml) stimulated mean gingival fibroblast cell number to 23.2% and 36.7% above controls, and reduced mean collagen production by 37.7% and 37.4% below controls, respectively; however, neither CsA nor M17 affected mean protein production in comparison to control cultures. Analyses of responses to CsA and M17 by ligand-accumulating and non-accumulating fibroblasts sorted out from the parent cultures did not provide consistent interstrain responses either by cells representing the upper quartile of fluorescence or cells representing the bottom quartiles of fluorescence. These data demonstrate that CsA is accumulated by gingival fibroblasts and that CsA and M17 are potent modulators of gingival fibroblast phenotype.
Section of Periodontology, College of Dentistry, The Ohio State University, Columbus 43210, USA.
A
A
Mariotti
T
T
Hassell
D
D
Jacobs
C J
CJ
Manning
A F
AF
Hefti
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects
D003524:Cyclosporins; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D008024:Ligands; D011506:Proteins; D016572:Cyclosporine; C051527:cyclosporine metabolite M17; D003094:Collagen