Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway.
Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway.
复制标题
痤疮丙酸杆菌通过 ROS-NLRP3 途径诱导髓核细胞焦亡，加速椎间盘退变
DOI：
10.1155/2021/4657014
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发表时间：
2021
影响因子：
--
通讯作者：
Jiang W
中科院分区：
文献类型：
--
作者：
Tang G;Han X;Lin Z;Qian H;Chen B;Zhou C;Chen Y;Jiang W
我们之前的研究证实了痤疮丙酸杆菌（P. acnes）的存在，这是一种低毒力厌氧细菌，潜伏在退变椎间盘（IVD）中，并且感染与 IVD 退变密切相关。我们探讨了痤疮丙酸杆菌是否会诱导髓核细胞（NPC）焦亡，这是一种比细胞凋亡更危险的细胞死亡过程，并通过焦亡产物白细胞介素-（IL-）1β和IL-18加速IVD变性。与痤疮丙酸杆菌共培养后，人类 NPC 以时间和剂量依赖性方式响应 IL-1β 和 IL-18 的过度表达，表现出 NOD 样受体 3 (NLRP3)、裂解的 IL-1β、裂解的 caspase-1 和裂解的 Gasdermin D 的显着上调。此外，当与焦亡NPC在transwell系统中共培养时，正常NPC中炎症因子和分解代谢酶的基因表达显着增加，并且当NPC焦亡被抑制时，不良反应被抑制。此外，将痤疮丙酸杆菌接种到大鼠的IVD中会导致NPC显着焦亡和显着的IVD变性。最后，NPC 与痤疮丙酸杆菌共培养可诱导活性氧 (ROS) 和 NLRP3 的过度表达，而抑制这两个因子可减少 NPC 焦亡。因此，痤疮丙酸杆菌通过ROS-NLRP3信号通路诱导NPC焦亡，并且焦亡的NPC引起IVD变性级联。针对痤疮丙酸杆菌诱导的鼻咽癌焦亡可能成为未来 IVD 变性的替代治疗策略。
Our previous study verified the occurrence of Propionibacterium acnes (P. acnes), a low-virulence anaerobic bacterium, latently residing in degenerated intervertebral discs (IVDs), and the infection had a strong association with IVD degeneration. We explored whether P. acnes induces nucleus pulposus cell (NPC) pyroptosis, a more dangerous cell death process than apoptosis, and accelerates IVD degeneration via the pyroptotic products interleukin- (IL-) 1β and IL-18. After coculturing with P. acnes, human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1β, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1β and IL-18 in a time- and dose-dependent manner. In addition, the gene expression of inflammatory factors and catabolic enzymes significantly increased in normal NPCs when cocultured with pyroptotic NPCs in a transwell system, and the adverse effects were inhibited when NPC pyroptosis was suppressed. Furthermore, inoculation of P. acnes into the IVDs of rats caused significant pyroptosis of NPCs and remarkable IVD degeneration. Finally, coculture of NPCs with P. acnes induced the overexpression of reactive oxygen species (ROS) and NLRP3, while inhibition of both factors reduced NPC pyroptosis. Therefore, P. acnes induces NPC pyroptosis via the ROS-NLRP3 signaling pathway, and the pyroptotic NPCs cause an IVD degeneration cascade. Targeting the P. acnes-induced pyroptosis of NPCs may become an alternative treatment strategy for IVD degeneration in the future.
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影响因子：
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