Premium
Expression of Matrix Metalloproteinases in Cyclosporin‐Treated Gingival Fibroblasts Is Regulated by Transforming Growth Factor (TGF)‐β1 Autocrine Stimulation
Author(s) -
Cotrim P.,
Andrade C.R.,
MartelliJunior H.,
Graner E.,
Sauk J.J.,
Coletta R.D.
Publication year - 2002
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2002.73.11.1313
Subject(s) - autocrine signalling , transforming growth factor , matrix metalloproteinase , fibroblast , pathogenesis , stimulation , chemistry , growth factor , microbiology and biotechnology , endocrinology , biology , immunology , in vitro , receptor , biochemistry
Background: Gingival overgrowth is a common side effect following the administration of cyclosporin A (CsA). 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‐β1 (TGF‐β1). The aim of this study was to investigate the potential role of TGF‐β1 in the pathogenesis of CsA‐induced gingival overgrowth, exploring a possible autocrine stimulation of TGF‐β1 as a cellular regulator of synthesis of matrix metalloproteinases (MMPs) and its tissue inhibitors (TIMPs). Methods: Gingival fibroblasts from human normal gingiva were incubated with increasing concentrations of CsA, cultured for 24 hours, and the expression and production of TGF‐β1 determined by semiquantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. MMP and TIMP mRNA expression levels were also analyzed by RT‐PCR. To determine the effect of TGF‐β1 on the expression of MMP and TIMP by human gingival fibroblasts under CsA treatment, human gingival fibroblast cultures were treated with sense oligonucleotides (SON) or antisense oligonucleotides (AON). Results: CsA simultaneously stimulated TGF‐β1 expression and production and inhibited expression of MMP‐1 and MMP‐2 by human gingival fibroblasts, whereas CsA has a slight effect on TIMP‐1 and TIMP‐2 expression. AON reduced TGF‐β1 production as demonstrated by ELISA, whereas TGF‐β1 mRNA expression levels were not significantly modified. The inhibition of TGF‐β1production byAONmodulated MMP expression, demonstrating the autocrine inhibitory effect of TGF‐β1 in CsA‐treated human gingival fibroblasts. Conclusions: The data presented here suggest that TGF‐β1 in an autocrine fashion may contribute to a reduction of proteolytic activity of human gingival fibroblasts in CsA‐induced gingival overgrowth, which favors the accumulation of extracellular matrix. J Periodontol 2002;73:1313‐1322.