Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway
Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway
复制标题
痤疮丙酸杆菌通过 TLR2-NF-κB/JNK 或 ROS 通路中 NGF 的上调导致腰痛
DOI：
10.1016/j.micinf.2022.104980
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发表时间：
2022-09-08
影响因子：
5.8
通讯作者：
Cao, Peng
中科院分区：
文献类型：
--
作者：
Jiao, Yucheng;Lin, Yazhou;Cao, Peng
椎间盘 (IVD) 中的痤疮丙酸杆菌感染是新发现的腰痛 (LBP) 原因。在本研究中，我们旨在确定神经生长因子（NGF）（一种关键的促痛因子）是否与痤疮丙酸杆菌诱导的腰痛有关。与痤疮丙酸杆菌共培养后，髓核细胞（NPC）产生NGF，将痤疮丙酸杆菌接种到大鼠IVD后，NGF上调。此外，将痤疮丙酸杆菌注射到大鼠IVD中会导致明显的机械异常性疼痛和冷反射亢进，以及大鼠背根神经节（DRG）中疼痛相关因子的显着上调，包括P物质（SP）、降钙素基因相关肽（CGRP）和瞬时受体电位香草酸1（TRPV1），表明痤疮丙酸杆菌接种的大鼠具有明显的盘源性LBP。然而，抑制 NGF 生物活性可显着改善痤疮丙酸杆菌诱导的盘源性腰痛，表明痤疮丙酸杆菌通过 NGF 诱导腰痛。最后，体外机制研究表明，痤疮丙酸杆菌通过TLR-2受体和NF-KB p65/JNK通路或ROS相关通路刺激NPC分泌NGF。因此，痤疮丙酸杆菌通过 TLR2-NF-KB/JNK 或 ROS 相关途径刺激 NPC 分泌 NGF，与 LBP 具有很强的相关性。这些发现提出了一种新的潜在 LBP 治疗策略。 (C) 2022 由 Elsevier Masson SAS 代表巴斯德研究所出版。
Propionibacterium acnes infection in intervertebral discs (IVDs) is a newly identified cause of low back pain (LBP). In the present study, we aimed to determine whether the nerve growth factor (NGF), a critical pro-algesic factor, is involved in P. acnes-induced LBP. After co-culturing with P. acnes, nucleus pulposus cells (NPCs) produced NGF, which was upregulated after inoculation of P. acnes into IVDs of rats. In addition, administration of P. acnes into rat IVDs leads to significant mechanical allodynia and cold hyperreflexia, and significant upregulation of the pain-related factors, including substance P (SP), calcitonin gene-related peptide (CGRP), and Transient Receptor Potential Vanilloid 1 (TRPV1), in rat dorsal root ganglia (DRG), suggesting that P. acnes-inoculated rats had obvious discogenic LBP. However, inhibition of NGF bioactivity significantly ameliorated P. acnes-induced discogenic LBP, suggesting that P. acnes induced LBP via NGF. Finally, an in vitro mechanism study demonstrated that P. acnes stimulated NPCs to secrete NGF via TLR-2 receptor and NF -KB p65/JNK pathway, or ROS-related pathway. Therefore, P. acnes had a strong association with LBP by stimulating NPCs to secrete NGF via the TLR2-NF-KB/JNK or ROS-related pathway. These findings propose a novel potential therapeutic strategy for LBP. (C) 2022 Published by Elsevier Masson SAS on behalf of Institut Pasteur.