scholarly journals Gamma‐secretase inhibitor suppressed Notch1 intracellular domain combination with p65 and resulted in the inhibition of the NF‐κB signaling pathway induced by IL‐1β and TNF‐α in nucleus pulposus cells

2018 ◽  
Vol 120 (2) ◽  
pp. 1903-1915 ◽  
Author(s):  
Yao Huang ◽  
Wei Mei ◽  
Jian Chen ◽  
Tao Jiang ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Gamma Secretase ◽  
Nucleus Pulposus Cells ◽  
Intracellular Domain ◽  
Domain Combination ◽  
Secretase Inhibitor ◽  
Tnf Α ◽  
Gamma Secretase Inhibitor

scholarly journals LIPUS inhibits inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Weiwei Yi ◽  
Qing Chen ◽  
Chuan Liu ◽  
Kaiting Li ◽  
Bailong Tao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Real Time ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Real Time Pcr ◽  
Inflammatory Factors ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Collagen Ii

Abstract Background Low-intensity pulsed ultrasound (LIPUS) is a safe and noninvasive rehabilitative physical therapy with anti-inflammatory effects. The current study investigated the effect of LIPUS on the inflammation of nucleus pulposus (NP) cells and its underlying mechanism. Methods Human NP cells were acquired from lumbar disc herniation tissue samples and cultured for experiments. Human NP cells were treated with LPS and then exposed to LIPUS (15 mW/cm2, 30 mW/cm2 and 60 mW/cm2) for 20 min daily for 3 days to determine the appropriate intensity to inhibit the expression of the inflammatory factors TNF-α and IL-1β. The gene and protein expression of aggrecan, collagen II, MMP-3 and MMP-9 was measured by real‐time PCR and western blotting, respectively. The activity of the nuclear factor‐kappa B (NF‐κB) pathway was examined by western blotting and immunofluorescence. After pretreatment with the NF-κB inhibitor PDTC, the expression of TNF-α, IL-1β, MMP-3 and MMP-9 was measured by real‐time PCR. Results LIPUS at intensities of 15 mW/cm2, 30 mW/cm2 and 60 mW/cm2 inhibited LPS-induced NP cell expression of the inflammatory factors TNF-α and IL-1β, especially at 30 mW/cm2. LIPUS significantly upregulated the gene and protein expression of aggrecan and collagen II and downregulated the gene and protein expression of MMP-3 and MMP-9 in LPS-induced NP cells. The NF‐κB signaling pathway was inhibited by LIPUS through inhibiting the protein expression of p-P65 and the translocation of P65 into the nucleus in LPS-induced NP cells. In addition, LIPUS had similar effects as the NF-κB inhibitor PDTC by inhibiting the NF-κB signaling pathway, inflammation and catabolism in LPS-induced human degenerative nucleus pulposus cells. Conclusion LIPUS inhibited inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells.

scholarly journals Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-κB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Haichao Yu ◽  
Guowei Hou ◽  
Jiankang Cao ◽  
Yanyu Yin ◽  
Yunpeng Zhao ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Nucleus Pulposus Cells ◽  
Mitochondrial Ros ◽  
Tnf Α

Intervertebral disc degeneration (IVDD), one of the most common clinical diseases worldwide, causes disc herniation and sciatica. Recent studies have identified the involvement of mitochondrial dysfunction, inflammatory responses, and extracellular matrix degradation in IVDD. Mangiferin is known to protect against various diseases by inhibiting oxidative stress, suppressing inflammation reaction, and relieving mitochondrial dysfunction. Whether mangiferin can alleviate IVDD remains to be elucidated. In the present study, human nucleus pulposus cells (HNPCs) and mouse intervertebral discs were cultured and stimulated with TNF-α, with or without treatment of mangiferin. Moreover, we established a rat needle puncture model and injected mangiferin into the intervertebral discs to verify its protective effect on IVDD. Furthermore, the activity of the NF-κB signaling pathway was tested in vitro. Our results indicated that mangiferin alleviated the inflammatory response and reversed the loss of major intervertebral disc components. Besides, mangiferin reduced reactive oxygen species production, ameliorated mitochondrial damage, and decreased the expression of apoptosis-related parameters in stimulation of TNF-α. In addition, mangiferin antagonized the activation of the NF-κB signaling pathway induced by TNF-α. Collectively, mangiferin antagonized mitochondrial ROS in NP cells and protected against IVDD by suppressing the activation of the NF-κB signaling pathway, which might provide a potential therapeutic instrument for IVDD.

scholarly journals LncRNA NEAT1 promotes nucleus pulposus cell matrix degradation through regulating Nrf2/ARE axis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Cheng Li ◽  
Xinjian Ma ◽  
Chenfei Ni ◽  
Jingyan Xu ◽  
Yinfei Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Matrix Degradation ◽  
Nucleus Pulposus Cells ◽  
Tnf Α ◽  
Healthy Control ◽  
Nrf2 Activator ◽  
Lncrna Neat1 ◽  
Nrf2 Expression

Abstract Background This study aimed to assess the role and mechanism of lncRNA NEAT1 in intervertebral disc degeneration (IVD). Methods LncRNA profile (GSE56081) between IVD and healthy control was downloaded from the Gene Expression Omnibus (GEO) database and analyzes differential lncRNA expression. Expression of lncRNA NEAT1 in IVD tissue and TNF-α/IL-1β-stimulated nucleus pulposus cells were further measured by RT-PCR. The lncRNA NEAT1 overexpression plasmids (pcDNA-NEAT1) were constructed and transfected into nucleus pulposus cells. Catabolic biomarkers (MMP-3 and MMP-13), anabolic biomarkers (Col II and Aggrecan) and Nrf2 expression were further measured. To further investigate the function of Nrf2, nucleus pulposus cells were pretreated with or without 25 μM tert-Butylhydroquinone (TBHQ), a Nrf2 activator, for 18 h and subsequently cotreated with pcDNA-NEAT1. Results A total of 1432 lncRNAs were differentially expressed in GSE56081. Bioinformatic analysis found that these lncRNAs mainly enriched in Nrf2/ARE signaling pathway. LncRNA NEAT1 was highly expressed in IVD tissues than that of healthy control. Moreover, TNF-α/IL-1β induced a time- and dose-dependent increase in the mRNA expression of lncRNA NEAT1 in the nucleus pulposus cells. Overexpression of lncRNA NEAT1 abates promotes nucleus pulposus cells proliferation but induces matrix degradation. Meanwhile, nucleus and cytoplasm Nrf2 expression was significantly down-regulated by lncRNA NEAT1 upregulation. Nrf2 activator (TBHQ) could partially reverse the inhibitory effects of overexpression of lncRNA NEAT1 on matrix degradation. Conclusion Collectively, our data unveiled the lncRNA NEAT1 promotes matrix degradation by regulating Nrf2/ARE signaling pathway, suggesting a potential therapeutic for IVD in the future.

scholarly journals Protective effects of ginsenoside Rg3 on TNF-α-induced human nucleus pulposus cells through inhibiting NF-κB signaling pathway

Life Sciences ◽  
2019 ◽  
Vol 216 ◽  
pp. 1-9 ◽  
Author(s):  
Jiang Chen ◽  
Gen-Zhe Liu ◽  
Qi Sun ◽  
Fan Zhang ◽  
Chu-yin Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Protective Effects ◽  
Ginsenoside Rg3 ◽  
Nucleus Pulposus Cells ◽  
Tnf Α

P1-180 Reduction in a-beta(1-40) and A-beta(1-42) in CSF and plasma in the beagle dog following acute oral dosing of the gamma secretase inhibitor, LY450139

2004 ◽  
Vol 25 ◽  
pp. S147 ◽  
Author(s):  
Paul A. Hyslop ◽  
Patrick C. May ◽  
James E. Audia ◽  
David O. Calligaro ◽  
Carl L. McMillian ◽  
...  
Keyword(s):  
Gamma Secretase ◽  
Oral Dosing ◽  
Beagle Dog ◽  
Secretase Inhibitor ◽  
Gamma Secretase Inhibitor

scholarly journals Intermittent Oral Coadministration of a Gamma Secretase Inhibitor with Dexamethasone Mitigates Intestinal Goblet Cell Hyperplasia in Rats

2013 ◽  
Vol 42 (2) ◽  
pp. 422-434 ◽  
Author(s):  
Shirley A. Aguirre ◽  
Ling Liu ◽  
Natilie A. Hosea ◽  
Wesley Scott ◽  
Jeffrey R. May ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Gamma Secretase ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Secretase Inhibitor ◽  
Gamma Secretase Inhibitor
Sign in / Sign up

Export Citation Format

Share Document