Resumen de Cyclosporin A Induces Proliferation in Human Gingival Fibroblasts via Induction of Transforming Growth Factor-β1
P. Cotrim, H. Martelli-Junior, E. Graner, John J. Sauk, Ricardo Della Coletta
Background: Cyclosporin A (CsA) is a widely used immunosuppressant that causes significant side effects including gingival overgrowth. The pathogenesis of this condition is not fully understood; however, recent studies show that CsA regulates the transcription of several cytokines including transforming growth factor-beta 1 (TGF-β1). In this study, we evaluated the effects of CsA and TGF-β1 on human normal gingival (NG) fibroblast proliferation, and explored a possible autocrine stimulation of TGF-β1 as a cellular regulator of proliferation induced by CsA in NG fibroblasts.
Methods: NG fibroblast cell lines were incubated with increasing concentrations of CsA or TGF-β1 and the proliferation index determined by automatic cell counting, BrdU incorporation, PCNA expression, and mitotic potential. To determine the effect of TGF-β1 on the proliferation rate of NG fibroblasts under CsA treatment, NG fibroblast cultures were simultaneously treated with CsA and antisense oligonucleotides against the translation-start site of the TGF-β1 mRNA.
Results: Treatment of NG fibroblasts with CsA or TGF-β1 significantly stimulated the cell proliferation in a dose-dependent manner. Furthermore, neutralization of TGF-β1 production in CsA-treated NG fibroblasts inhibited CsA’s effect on NG fibroblast proliferation, demonstrating an autocrine stimulatory effect of TGF-β1 in CsA-treated NG fibroblast proliferation.
Conclusion: The results presented here suggest that CsA stimulatory induction of NG fibroblast proliferation is mediated via TGF-β1 in an autocrine fashion. J Periodontol 2003;74:1625-1633.
