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
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
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DOI：
10.3892/ijmm_2018.3714
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发表时间：
2018-06
影响因子：
5.4
通讯作者：
Maiko Ohta;N. Chosa;S. Kyakumoto;Seiji Yokota;N. Okubo;A. Nemoto;M. Kamo;S. Joh;K. Satoh;A. Ishisaki
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文献类型：
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作者：
Maiko Ohta;N. Chosa;S. Kyakumoto;Seiji Yokota;N. Okubo;A. Nemoto;M. Kamo;S. Joh;K. Satoh;A. Ishisaki
牙周膜（PDL）中的机械敏感（MS）神经元在受到牙齿的机械刺激时将信息传递到三叉神经节。在牙周膜组织的咬合牙创伤过程中，MS神经元受到损伤，导致神经突起萎缩，最终导致MS神经元变性。神经生长因子（NGF）是一种神经营养因子，在受损感觉神经元的再生中起重要作用。在本研究中，我们观察了促炎细胞因子白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）对转化生长因子β1（TGF-β1）诱导的大鼠PDL源性SCDC 2细胞中NGF表达的影响。TGF-β1通过激活Smad 2/3和p38丝裂原活化蛋白激酶（MAPK）促进NGF表达。IL-1β和TNF-α抑制TGF-β1诱导的Smad 2/3和p38 MAPK的激活，导致NGF表达消失。TGF-β1处理的SCDC 2细胞分泌的NGF促进大鼠嗜铬细胞瘤PC 12细胞突起的延伸和酪氨酸羟化酶的表达，酪氨酸羟化酶是多巴胺合成的限速酶。这些结果提示，促炎细胞因子通过抑制TGF-β诱导的Smad 2/3和p38 MAPK信号通路，抑制TGF-β介导的PDL成纤维细胞NGF表达，可能导致PDL损伤神经元再生障碍。
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.