Cyclosporin-A Activated Latent TGF-β through Reactive Oxygen Species in Gingival Epithelial Cells
Objectives: Transforming growth factor β (TGF-β) is a key regulator associated with pathogenesis of gingival overgrowth. Cyclosporin-A (CsA) has been shown to induce gingival overgrowth through TGF-β signaling pathway. However, the mechanisms of CsA-induced latent TGF-β1 activation is still unknown. The aim of this study were to investigate the mechanisms of CsA activates latent TGF-β1 and the role of reactive oxygen species (ROS) in CsA-induced TGF-β1 activation in human gingival epithelium (hGE) cells. Methods: Effects of CsA on epithelial-to mesenchymal transition (EMT), Smad3 phosphorylation and activated-TGF-β1 levels in two hGE cells (OECM-1 and CA9-22) were assessed by Western blot analysis and enzyme-linked immunosorbent assay. Results: The expression of E-cadherin decreased and slug increased after 48 hours treatment with CsA in OECM-1 and CA9-22 cells. CsA induced Smad3 phosphorylation by TGF-β1 activation in OECM-1 and CA9-22 cells. Pretreatment with N-acetyl-cystenine (reactive oxygen species (ROS) inhibitor), Diphenylene iodonium (NOX inhibitor), Plumbagin (NOX4 inhibitor), Apocynine (NOX2 inhibitor), curcumin, EGCG, lovastatin in OECM-1 and CA9-22 cells significantly inhibited CsA-induced TGF-β1 activation. Moreover, curcumin dose-dependently inhibited CsA-induced latent TGF-β1 activation in OECM-1 and CA9-22 cells. Conclusions: CsA induced latent TGF-β1 activation via NOX2 and NOX4-derived ROS generation in hGE cells. Curcumin significantly inhibited CsA-induced latent TGF-β1 activation in hGE cells and could be a potential therapy of gingival overgrowth.
South East Asia Division Meeting
2018 South East Asia Division Meeting (Da Nang, Vietnam) Da Nang, Vietnam
2018 0187 Periodontal Research - Therapy
Huang, Chen-pang
( National Taiwan University
, Taipei
, Taiwan
; National Taiwan University Hospital
, Taipei
, Taiwan
)
Kuo, Mark Yen-ping
( National Taiwan University
, Taipei
, Taiwan
; National Taiwan University Hospital
, Taipei
, Taiwan
)
Chen, Yi-wen
( National Taiwan University
, Taipei
, Taiwan
; National Taiwan University Hospital
, Taipei
, Taiwan
)