Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin.
Inflammation
; 43(3): 796-809, 2020 Jun.
Article
en En
| MEDLINE
| ID: mdl-31900828
ABSTRACT
Intervertebral disc degeneration (IDD) is characterized by an imbalance between matrix synthesis and degradation in intervertebral discs. However, the causes of this imbalance remain elusive. Previous studies revealed that NLRP3 inflammasome plays a vital role in IDD and nicotinamide phosphoribosyl transferase (NAMPT) is involved in matrix degradation induced by IL-1ß. In the current study, real-time PCR, western blot and NAMPT knockdown, or overexpression experiments were used to detect the regulatory effects of NAMPT on NLRP3 inflammasome activity in nucleus pulposus (NP) cells. The results revealed that NAMPT downregulation or overexpression controlled the matrix degradation induced by TNF-α by modulating NLRP3 inflammasome activity. Moreover, the NAMPT inhibition study demonstrated MAPK and NF-κB signaling play a key role in above process. In addition, melatonin was reported to play a protective role in matrix metabolism of NP cells. Herein, real-time PCR, western blot analysis, and immunofluorescence staining experiments revealed that melatonin showed protective effects against TNF-α-induced matrix degradation by downregulating NAMPT and reducing NLRP3 inflammasome activity in NP cells. The current investigation verified that melatonin could alleviate matrix degradation induced by TNF-α by suppressing NAMPT and NLRP3 inflammasome activity. Moreover, NAMPT downregulation controlled the matrix degradation induced by TNF-α by suppressing NLRP3 inflammasome activity through MAPK and NF-κB signaling in NP cells.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Citocinas
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FN-kappa B
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Sistema de Señalización de MAP Quinasas
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Nicotinamida Fosforribosiltransferasa
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Núcleo Pulposo
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Proteína con Dominio Pirina 3 de la Familia NLR
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Melatonina
Límite:
Animals
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article