Therapeutic potential of proteasome inhibitors for dihydropyridine-induced gingival overgrowth

Sao Lun Lu, Jui Hung Chang, Chiung Fang Huang, Li Sheng Chen

Research output: Contribution to journalArticle

Abstract

Objectives: NF-κB plays a crucial role in collagen overproduction in dihydropyridine-induced gingival overgrowth (DIGO) fibroblasts. We aim to investigate the role of the kappa B (IκB) kinase (IKK)–NF-κB pathway and downstream collagen type I (Col I) synthesis in DIGO cells and to demonstrate the therapeutic strategy of interference of this pathway with proteasome inhibitors. Methods: Gingival fibroblasts from DIGO (n = 5) and healthy (n = 5) patients were selected and stimulated with IL-1β, nifedipine, or both. All experiments were run in triplicate and independently for each primary cell sample. Results: The results demonstrated that both drugs additively mediated NF-κB activity by activating IKKα/β phosphorylation. They also triggered nuclear translocation of NF-κB, Rela, and p50 (*p <.05) and increased Col I production in both healthy and DIGO cells. The addition of proteasome inhibitors, including bortezomib and MG132, promoted the accumulation of phosphorylated p-IκBα, prevented the subsequent cytosol-to-nuclear translocation of p50 and Rela (*p <.05), and abbreviated the biosynthesis of Col I in DIGO cells. Conclusions: We suggested that IKK–IκBα activation is mediated by proinflammatory cytokines and CCBs in DIGO cells and triggers downstream NF-κB–Col I synthesis. Proteasome inhibitors may strategically interfere with the IKK–IκBα–NF-κB–Col I pathway and inhibit the etiopathogenesis of DIGO.

Original languageEnglish
JournalOral Diseases
Volume26
Issue number3
DOIs
Publication statusPublished - Apr 1 2020

Keywords

  • canonical NF-κB pathway
  • collagen type I
  • IL-1β
  • inflammation
  • nifedipine
  • proteasome inhibitor

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)

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