Nicotinamide Phosphoribosyl Transferase Controls NLRP3 Inflammasome Activity Through MAPK and NF-κB Signaling in Nucleus Pulposus Cells, as Suppressed by Melatonin

• Published in: Inflammation 2020-06, Vol.43 (3), p.796-809
• Main Authors: Huang, Yingjie, Peng, Yan, Sun, Jianchao, Li, Shuangxing, Hong, Junmin, Zhou, Jie, Chen, Jianchong, Yan, Jiansen, Huang, Zhengqi, Wang, Xiaofei, Chen, Weijian, Ye, Wei
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Degeneration; Degradation; Humans; IL-1β; Immunofluorescence; Immunology; Inflammasomes; Internal Medicine; Intervertebral discs; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Melatonin; Melatonin - pharmacology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB protein; Nicotinamide; Nicotinamide Phosphoribosyltransferase - antagonists & inhibitors; Nicotinamide Phosphoribosyltransferase - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nucleus pulposus; Nucleus Pulposus - cytology; Nucleus Pulposus - drug effects; Nucleus Pulposus - metabolism; Original Article; Pathology; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Rheumatology; Tumor Necrosis Factor-alpha - toxicity; Tumor necrosis factor-α
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-019-01166-z

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-1β. 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.