IL‑1β and TNF‑α suppress TGF‑β‑promoted NGF expression in periodontal ligament‑derived fibroblasts through inactivation of TGF‑β‑induced Smad2/3‑ and p38 MAPK‑mediated signals

Ohta,Maiko; Chosa,Naoyuki; Kyakumoto,Seiko; Yokota,Seiji; Okubo,Naoto; Nemoto,Akira; Kamo,Masaharu; Joh,Shigeharu; Satoh,Kenichi; Ishisaki,Akira

doi:10.3892/ijmm.2018.3714

IL‑1β and TNF‑α suppress TGF‑β‑promoted NGF expression in periodontal ligament‑derived fibroblasts through inactivation of TGF‑β‑induced Smad2/3‑ and p38 MAPK‑mediated signals

Authors:
- Maiko Ohta
- Naoyuki Chosa
- Seiko Kyakumoto
- Seiji Yokota
- Naoto Okubo
- Akira Nemoto
- Masaharu Kamo
- Shigeharu Joh
- Kenichi Satoh
- Akira Ishisaki
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Affiliations: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Shiwa‑gun, Iwate 028‑3694, Japan, Laboratory of Pathophysiology and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita‑ku, Sapporo 060‑0812, Japan, Division of Operative Dentistry and Endodontics, Department of Conservative Dentistry, Iwate Medical University, Morioka, Iwate 020‑8505, Japan, Division of Oral and Dysphasia Rehabilitation, Department of Prosthodontics, Iwate Medical University, Morioka, Iwate 020‑8505, Japan, Division of Dental Anesthesia, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University, Morioka, Iwate 020‑8505, Japan
Published online on: June 4, 2018 https://doi.org/10.3892/ijmm.2018.3714
Pages: 1484-1494
Copyright: © Ohta et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mechanosensitive (MS) neurons in the periodontal ligament (PDL) pass information to the trigeminal ganglion when excited by mechanical stimulation of the tooth. During occlusal tooth trauma of PDL tissues, MS neurons are injured, resulting in atrophic neurites and eventual degeneration of MS neurons. Nerve growth factor (NGF), a neurotrophic factor, serves important roles in the regeneration of injured sensory neurons. In the present study, the effect of pro‑inflammatory cytokines, including interleukin 1β (IL‑1β) and tumor necrosis factor α (TNF‑α), on transforming growth factor β1 (TGF‑β1)‑induced NGF expression was evaluated in rat PDL‑derived SCDC2 cells. It was observed that TGF‑β1 promoted NGF expression via Smad2/3 and p38 mitogen‑activated protein kinase (MAPK) activation. IL‑1β and TNF‑α suppressed the TGF‑β1‑induced activation of Smad2/3 and p38 MAPK, resulting in the abrogation of NGF expression. NGF secreted by TGF‑β1‑treated SCDC2 cells promoted neurite extension and the expression of tyrosine hydroxylase, a rate‑limiting enzyme in dopamine synthesis in rat pheochromocytoma PC12 cells. These results suggested that pro‑inflammatory cytokines suppressed the TGF‑β‑mediated expression of NGF in PDL‑derived fibroblasts through the inactivation of TGF‑β‑induced Smad2/3 and p38 MAPK signaling, possibly resulting in the disturbance of the regeneration of injured PDL neurons.

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