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- Title
Therapeutic potential of proteasome inhibitors for dihydropyridine‐induced gingival overgrowth.
- Authors
Lu, Sao‐Lun; Chang, Jui‐Hung; Huang, Chiung‐Fang; Chen, Li‐Sheng
- 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.
- Subjects
THERAPEUTIC use of protease inhibitors; CELLULAR signal transduction; CLINICAL trials; GINGIVAL hyperplasia; INFLAMMATION; INTERLEUKINS; NIFEDIPINE; PYRIDINE; WESTERN immunoblotting; DNA-binding proteins; TREATMENT effectiveness; DESCRIPTIVE statistics
- Publication
Oral Diseases, 2020, Vol 26, Issue 3, p630
- ISSN
1354-523X
- Publication type
Article
- DOI
10.1111/odi.13260