Propionibacterium acnes Accelerates Intervertebral Disc Degeneration by Inducing Pyroptosis of Nucleus Pulposus Cells via the ROS-NLRP3 Pathway.
Oxid Med Cell Longev
; 2021: 4657014, 2021.
Article
en En
| MEDLINE
| ID: mdl-33603947
ABSTRACT
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-) 1ß and IL-18. After coculturing with P. acnes, human NPCs showed significant upregulation of NOD-like receptor 3 (NLRP3), cleaved IL-1ß, cleaved caspase-1, and cleaved gasdermin D in response to the overexpression of IL-1ß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propionibacterium acnes
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Transducción de Señal
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Especies Reactivas de Oxígeno
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Degeneración del Disco Intervertebral
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Piroptosis
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Núcleo Pulposo
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Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Oxid Med Cell Longev
Asunto de la revista:
METABOLISMO
Año:
2021
Tipo del documento:
Article
País de afiliación:
China