Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and inflammation in cyclosporine a-induced gingival enlargement: A pilot in vitro study using a three-dimensional model of the human oral mucosa

Matthew Johanson, Xiang R. Zhao, Guy Huynh-Ba, Cristina C. Villar

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: It has been suggested that cyclosporine A (CsA) induces gingival enlargement by promoting an increase in the gingival extracellular matrix (ECM). Nonetheless, the variable occurrence of CsA-induced gingival enlargement in patients receiving this medication indicates a multifactorial pathogenesis. Clinical observations suggest that local inflammation is associated with the development and severity of CsA-induced gingival enlargement. Therefore, the purpose of this study is to investigate the effects of CsA and inflammation on the production of ECM homeostatic mediators. Methods: The effects of CsA and inflammation (as assessed using interleukin [IL]-1β) on the secretion of mediators involved in ECM homeostasis were determined using fibroblast monolayers and three-dimensional (3D) models of the human oral mucosa. Fibroblast monolayers and 3D cultures were treated with CsA alone or in combination with IL-1b for up to 72 hours, and the secretion of matrix metalloproteinases (MMPs) 1, 2, 3, 8, 9, 10, and 13 and tissue inhibitors of MMPs (TIMPs) 1, 2, and 4 into the culture medium was assessed using enzyme-linked immunoassay-based antibody arrays. Results: Fibroblast monolayers responded to CsA with no changes in the secretion of ECM mediators. Conversely, 3D cultures responded to CsA treatment with a reduction in MMP-10 secretion. IL-1b alone triggered higher secretory levels of MMPs in both fibroblast monolayers (MMP-3 and MMP-10) and 3D cultures (MMP-9 and MMP-10). Importantly, fibroblast monolayers and 3D cultures treated with a combination of IL-1b and CsA showed a decrease in the MMP-1/TIMP-1 ratio. Conclusions: These data support the hypothesis that inflammation may alter the pathogenesis of CsA-induced gingival enlargement by promoting a synergistic decrease in the MMP-1/TIMP-1 ratio.

Original languageEnglish (US)
Pages (from-to)634-640
Number of pages7
JournalJournal of periodontology
Volume84
Issue number5
DOIs
StatePublished - Apr 1 2013

Keywords

  • Collagen
  • Cyclosporine
  • Gingival overgrowth
  • Inflammation
  • Metalloproteases
  • Tissue inhibitor of metalloproteinases

ASJC Scopus subject areas

  • Periodontics

Fingerprint Dive into the research topics of 'Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and inflammation in cyclosporine a-induced gingival enlargement: A pilot in vitro study using a three-dimensional model of the human oral mucosa'. Together they form a unique fingerprint.

  • Cite this