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抑制 TNFR1 通过调控 NF-κB 和 MAPK 信号通路减轻 LPS 诱导的人椎间盘细胞凋亡和炎症反应。

Inhibition of TNFR1 Attenuates LPS Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Regulating the NF-KB and MAPK Signalling Pathway.

机构信息

Department of Pain, Zibo Central Hospital, No. 54 The communist youth league road, Zibo, 255000, Shandong Province, People's Republic of China.

Department of Orthopedics, ShanDong Energy ZiBo Mining Group Co.LTD. Central Hospital, Zibo, 255120, Shandong, People's Republic of China.

出版信息

Neurochem Res. 2021 Jun;46(6):1390-1399. doi: 10.1007/s11064-021-03278-1. Epub 2021 Mar 13.

Abstract

Intervertebral disc degeneration (IDD) is accompanied by nucleus pulposus (NP) cell apoptosis, inflammation, and extracellular matrix degradation. Tumour necrosis factor receptor 1 (TNFR1) is a receptor of TNF-α, and is deeply involved in the processes of IDD. However, the effect of TNFR1 inhibition on IDD is not clear. Herein, we report that TNFR1 was increased in LPS-treated HNPCs. The aim of this study was to investigate the potential therapeutic effect of TNFR1 siRNA and selective antagonists of TNFR1 (GSK1995057) on HNPC damage. The results showed that the blockade of TNFR1 by TNFR1 siRNA and GSK1995057 effectively suppressed the cell viability loss, apoptosis, and inflammation induced by LPS in HNPCs. Furthermore, we found that TNFR1 siRNA and GSK1995057 inhibited activation of the NF-KB and MAPK signalling pathways in LPS-stimulated HNPCs. In summary, the blockade of TNFR1 effectively suppressed LPS-induced apoptosis and inflammation in HNPCs through the NF-KB and MAPK signalling pathways. This revealed that the blockade of TNFR1 may provide a potential therapeutic treatment for IDD.

摘要

椎间盘退变(IDD)伴随着髓核(NP)细胞凋亡、炎症和细胞外基质降解。肿瘤坏死因子受体 1(TNFR1)是 TNF-α的受体,其在 IDD 过程中深度参与。然而,TNFR1 抑制对 IDD 的影响尚不清楚。在此,我们报道 LPS 处理的 HNPCs 中 TNFR1 增加。本研究旨在探讨 TNFR1 siRNA 和 TNFR1 选择性拮抗剂(GSK1995057)对 HNPC 损伤的潜在治疗作用。结果表明,TNFR1 siRNA 和 GSK1995057 通过阻断 TNFR1 可有效抑制 LPS 诱导的 HNPC 活力丧失、凋亡和炎症。此外,我们发现 TNFR1 siRNA 和 GSK1995057 抑制了 LPS 刺激的 HNPC 中 NF-KB 和 MAPK 信号通路的激活。总之,通过 NF-KB 和 MAPK 信号通路,阻断 TNFR1 可有效抑制 LPS 诱导的 HNPC 凋亡和炎症。这表明阻断 TNFR1 可能为 IDD 提供一种潜在的治疗方法。

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