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

Huang, Yingjie; Peng, Yan; Sun, Jianchao; Li, Shuangxing; Hong, Junmin; Zhou, Jie; Chen, Jianchong; Yan, Jiansen; Huang, Zhengqi; Wang, Xiaofei; Chen, Weijian; Ye, Wei

doi:10.1007/s10753-019-01166-z

Cited by 49 publications

(27 citation statements)

References 43 publications

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“…In infected macrophages, the number of overlapping DEGs and enriched pathways were very high between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups, suggesting that homeostasis of dam expression was essential for Salmonella virulence and the ability to induce inflammasome activation. The MAPK signaling pathway [48], TGF-β signaling pathway [49], TNF signaling pathway [50,51], and FoxO signaling pathway [52] from overlapping enriched pathways were all reported to be related to the activation of inflammasome. The transcription regulator c-Fos plays an important role in regulating multiple signal pathways including MAPK and TNF [53].…”

Section: Discussionmentioning

confidence: 99%

Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

Guo

Huang

et al. 2020

BMC Microbiol

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Background: Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. Given that the inflammasomes play an essential role in resisting bacterial infection, Salmonella has evolved various strategies to regulate activation of the inflammasome, most of which largely remain unclear. Results: A transposon mutant library in SE strain C50336 was screened for the identification of the potential factors that regulate inflammasome activation. We found that T3SS-associated genes invC, prgH, and spaN were required for inflammasome activation in vitro. Interestingly, C50336 strains with deletion or overexpression of Dam were both defective in activation of caspase-1, secretion of IL-1β and phosphorylation of c-Jun N-terminal kinase (Jnk). Transcriptome sequencing (RNA-seq) results showed that most of the differentially expressed genes and enriched KEGG pathways between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups overlapped, which includes multiple signaling pathways related to the inflammasome. C50336Δdam and C50336::dam were both found to be defective in suppressing the expression of several anti-inflammasome factors. Moreover, overexpression of Dam in macrophages by lentiviral infection could specifically enhance the activation of NLRP3 inflammasome independently via promoting the Jnk pathway. Conclusions: These data indicated that Dam was essential for modulating inflammasome activation during SE infection, there were complex and dynamic interplays between Dam and the inflammasome under different conditions. New insights were provided about the battle between SE and host innate immunological mechanisms.

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Section: Discussionmentioning

confidence: 99%

Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

Guo

Huang

et al. 2020

BMC Microbiol

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“…106 The NAMPT inhibitor, APO866, can reverse the matrix degradation induced by IL-1β in NP cells through autophagy. 107 Huang et al 108 showed that the downregulation of NAMPT controls TNFα-induced NLRP3 inflammasome activity and NP matrix degradation by inhibiting NF-κB signalling. TGF-β1 has been shown to promote the proliferation of NP cells, stimulate ECM synthesis, reduce the expression of ADAMTS and increase the expression of tissue metalloproteinase (TIMP), and TIMP is an inhibitor of MMP and ADAMTS.…”

Section: Factorsthatinhibitnf-κbiniddmentioning

confidence: 99%

NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration

et al. 2021

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Intervertebral disc degeneration (IDD) is a common degenerative disease of the musculoskeletal system and is also the main cause of chronic low back pain (LBP), which seriously affects the quality of life of patients and places a huge economic burden on families and society. [1][2][3] It is estimated that about 20% of adolescents have mild IDD and 80% of the general population will experience back pain symptoms during their lifetime. 4 However, the specific pathogenesis of IDD is still not fully understood. At present, IDD is believed to be a complex cell-mediated process that ultimately leads to changes in intervertebral disc (IVD) structure and function. 5

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“…Inflammasomes were multiprotein signaling platforms that controlled the inflammatory responses 15 and coordinated antimicrobial host defenses. Previous studies demonstrated that NLRP3 inflammasome plays a vital role in IDD; 16 however, no previous study focused the effect of cGAS/Sting pathway on NLRP3 inflammasome activation in the development of IDD.…”

Section: Introductionmentioning

confidence: 97%

Epigallocatechin-3-Gallate Protects H2O2-Induced Nucleus Pulposus Cell Apoptosis and Inflammation by Inhibiting cGAS/Sting/NLRP3 Activation

Tian

Bao

et al. 2020

DDDT

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Background: Intervertebral disc degeneration (IDD) is the most common diagnosis of patients with lower back pain. IDD is the underlying lesion of many spinal degenerative diseases; however, the role of cGAS/Sting/NLRP3 pathway and epigallocatechin gallate (EGCG) in the development of IDD remained unclear. Methods: The expressions of cGAS, Sting and NLRP3 mRNA of intervertebral disc (IVD) samples from IDD patients and controls were detected by RT-PCR. The nucleus pulposus cells (NPCs) were induced by hydrogen peroxide (H 2 O 2 ) and used as an in-vitro model. Both 5 μM and 25 μM EGCG treatment were used to detect the effect of EGCG on the in-vitro model. Cell viability was detected by the MTT method, and cell apoptosis and cell cycle would be detected by flow cytometry. Western blot was used in the detection of the expression of cGAS/Sting/NLRP3 as well as apoptosis-related protein level. ELISA was used in the detection of pro-inflammatory factors, including IL-1β, TNF-α, IL-6 and IL-10. Results: The expressions of cGAS, Sting and NLRP3 mRNA were significantly increased in the IVD samples from IDD patients and NLRP3 was associated with cGAS and Sting. Advanced in-vitro study showed that H 2 O 2 significantly increased the expression of cGAS, Sting and NLRP3 protein levels. Advanced experiments showed that EGCG treatment demonstrated significant protective effects in cell viability, apoptosis, cell cycle arrest and inflammatory status through down-regulation of cGAS/Sting/NLRP3 pathway. Conclusion: It was shown that the cGAS, Sting and NLRP3 up-regulation was associated with the incidence of IDD. Our findings also suggest that EGCG treatment would provide anti-apoptosis, anti-inflammation and promote cell viability in H 2 O 2 treatment-incubated NPCs through inhibiting cGAS/Sting/NLRP3 pathway.

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

Cited by 49 publications

References 43 publications

Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration

<p>Epigallocatechin-3-Gallate Protects H<sub>2</sub>O<sub>2</sub>-Induced Nucleus Pulposus Cell Apoptosis and Inflammation by Inhibiting cGAS/Sting/NLRP3 Activation</p>

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