IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway

Ge, Jun; Qi, Yan; Wang, Yingjie; Cheng, Xiaoqiang; Song, Dawei; Wu, Cenhao; Yu, Hao; Yang, Huilin; Zou, Jun

doi:10.1016/j.freeradbiomed.2019.12.040

Cited by 55 publications

(45 citation statements)

References 35 publications

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“…New primary NPCs were isolated and subcultured to the 3rd generation before each experiment (including repeated experiments). The method of culture of primary NPCs was consistent with our previous protocol (Ge et al, 2020a). NPC were cultured in DMEM medium supplemented with 10% (v/v) fetal bovine serum, 100 U/ml penicillin, 100 mg/ml streptomycin, and 1% NPCs Growth Supplement (ScienCell, Carlsbad, CA, United States) at 37 • C and 5% CO2.…”

Section: Isolation and Culture Of Primary Nucleus Pulposus Cellsmentioning

confidence: 99%

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FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

Wang

et al. 2020

Front. Cell Dev. Biol.

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BackgroundIntervertebral disk (IVD) degeneration is the most common cause of lower back pain. Inhibiting inflammation is a key strategy for delaying IVD degeneration. Tacrolimus (FK506) is a potent immunosuppressive agent that is also beneficial to chondrocytes via alleviating inflammation. However, the potential function of FK506 in IVD and the underlying mechanisms remain unknown. The current study is aim at exploring the underlying mechanism of FK506 in preventing IVD degeneration.MethodsCell morphology was imaged using an optical microscope. mRNA levels of nucleus pulposus (NP) matrix components were determined by qRT-PCR, and protein expression NP matrix components was assessed by western blotting. A rat caudal IVD degeneration model was established to test for FK506 in vivo.ResultsFK506 improved the morphology of NP cells and the cell function at both the mRNA and protein level. FK506 could attenuate NP degeneration induced by IL-1β. Furthermore, FK506 exerted its function via TGFβ/Smad3 activation instead of through calcineurin inhibition. Inhibition of the TGF-β pathway prevented the protective effect of FK506 on IVD degeneration. In an in vivo study, FK506 injection reversed the development of rat caudal IVD degeneration influenced by Smad3.ConclusionOur current study demonstrates the positive effect of FK506 on delaying the degeneration of IVD via the TGFβ/Smad3 pathway.

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Section: Isolation and Culture Of Primary Nucleus Pulposus Cellsmentioning

confidence: 99%

“…qRT-PCR was performed in accordance with our previous protocol (Ge et al, 2020a). Total RNA from cells was extracted using the RNeasy kit (QIAGEN, Hilden, Germany).…”

Section: Qrt-pcrmentioning

confidence: 99%

FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

Wang

et al. 2020

Front. Cell Dev. Biol.

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“…Dephosphorylation of MAPK3/1 (ERK1/2) inhibits cell proliferation and differentiation [80]. In addition, this study showed that the expression level of Grb2 was downregulated after B. microti infection in mice and returned to a normal level on 19 d. The reduction in the Grb2 expression level reduced the abilities of various cytokines in response to the induction of proliferation signal transduction [81].…”

Section: Growth and Development-related Proteinsmentioning

confidence: 86%

Protein Regulation Strategies of Mouse Spleen in Response to Babesia Microti Infection

Xue

Ren

Masoudi

et al. 2020

Preprint

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BackgroundBabesia is a protozoan parasite in red blood cells of some vertebrates. Some species of Babesia can cause zoonoses and cause great harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured, but it still actively initiates immunomodulatory responses.MethodsIn order to explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and changes in phosphorylation modification in spleen tissue after Babesia microti infection in mice.ResultsAfter the mice were infected with B. microti, their spleen were seriously damaged.Using bioinfor-matics methods to analyze the dynamic changes of a large number of proteins, we found that spleen still initiated immune response to deal with the infection, in which immune-related proteins played an important role, including CTSD, IFI44, ILF2, ILF, and STAT5A. In addition, some proteins related to iron metabolism were also involved in the repair of spleen against B. microti infection, including serotransferrin, lactoferrin, TfR1, and GCL. At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including PKC-δ and MAPK3/1, Grb2, and PAK2. ConclusionsImmune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important important role in the regulation of spleen injury and maintenance of homeostasis. This study will provide important bases for the diagnosis and treatment of babesiosis.

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“…Human NP cells (ScienCell, USA) was cultured at specific medium containing 10% fetal bovine serum (FBS), 1% NP cell growth supplement and 1% penicillin/streptomycin in 5% CO 2 at 37°C (ScienCell, USA). When cells adhered to the wall up to 80%, IL-1β (Reprotech, USA) was added into the medium to induce degeneration of NP cells for 24 hours, the concentration of which was 10 ng/mL as described in previous studies [ 7 , 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

et al. 2020

Med Sci Monit

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Background Disc degeneration is characterized partly by the degradation in the extracellular matrix (ECM) and excess apoptosis of nucleus pulposus (NP) cells. NLRX1 (nucleotide-binding, leucine-rich repeat containing X1) is different from the other nucleotide-binding-domain and leucine-rich-repeat proteins and mainly located to the mitochondrial. It negatively regulates NF-κB (nuclear factor kappa B) and apoptosis inhibition. However, how NLRX1 is regulated and exerts effects in disc degeneration is unclear. Thus, the study aimed to analyze the effects of NLRX1 on NP cells. Material/Methods NLRX1 expression was detected in interleukin (IL)-1β-induced NP cells by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Then, NLRX1 was overexpressed in IL-1β-induced NP cells to detect apoptosis-related proteins and the extracellular matrix (ECM) by western blot, along with the detection of apoptosis levels using flow cytometry. StarBase predicted miR-423-5p target 3′UTR of NLRX1. Dual luciferase reporter assay showed that miR-423-5p could bind to the 3′UTR of NLRX1. Besides, miR-423-5p significantly affected NLRX1 levels detected by qRT-qPCR. Results The miR-423-5p overexpression markedly, and negatively regulated the protective effects of NLRX1 on IL-1β induced NP cells. Thus, our results suggested that miR-423-5p mediated the regulation of NLRX1 to affect apoptosis and ECM levels in IL-1β induced NP cells. Conclusions miR-423-5p and NLRX1 could be potential therapeutic targets for patients with disc degeneration.

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IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway

Cited by 55 publications

References 35 publications

FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

FK506 Induces the TGF-β1/Smad 3 Pathway Independently of Calcineurin Inhibition to Prevent Intervertebral Disk Degeneration

Protein Regulation Strategies of Mouse Spleen in Response to Babesia Microti Infection

MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

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