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Type: Artigo de periódico
Title: Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor-beta 1
Author: Cotrim, P
Martelli, H
Graner, E
Sauk, JJ
Coletta, RD
Abstract: 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-beta1). In this study, we evaluated the effects of CsA and TGF-beta1 on human normal gingival (NG) fibroblast proliferation, and explored a possible autocrine stimulation of TGF-beta1 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-beta1 and the proliferation index determined by automatic cell counting, BrdU incorporation, PCNA expression, and mitotic potential. To determine the effect of TGF-beta1 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-beta1 mRNA. Results: Treatment of NG fibroblasts with CsA or TGF-beta1 significantly stimulated the cell proliferation in a dose-dependent manner. Furthermore, neutralization of TGF-beta1 production in CsA-treated NG fibroblasts inhibited CsA's effect on NG fibroblast proliferation, demonstrating an autocrine stimulatory effect of TGF-beta1 in CsA-treated NG fibroblast proliferation. Conclusion: The results presented here suggest that CsA stimulatory induction of NG fibroblast proliferation is mediated via TGF-beta1 in an autocrine fashion.
Subject: Cyclosporin A/adverse effects
gingival hyperplasia/pathogenesis
growth factors
Country: EUA
Editor: Amer Acad Periodontology
Citation: Journal Of Periodontology. Amer Acad Periodontology, v. 74, n. 11, n. 1625, n. 1633, 2003.
Rights: fechado
Identifier DOI: 10.1902/jop.2003.74.11.1625
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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