FasL Expression on Human Nucleus Pulposus Cells Contributes to the Immune Privilege of Intervertebral Disc by Interacting with Immunocytes

Liu, Zhi-Heng; Sun, Zhen; Wang, Hai-Qiang; Ge, Jun; Jiang, Tongtong; Chen, Yufei; Ma, Ying; Wang, Chen; Hu, Sheng; Samartzis, D; Luo, Zhuojing

doi:10.7150/ijms.6223

Cited by 33 publications

(34 citation statements)

References 44 publications

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“…PF exhibits pharmacological activity, including antioxidant, anti-inflammatory and neuroprotective effects, on various types of cells (17)(18)(19) proliferation of annulus fibrosus cells and inhibited FasL-induced apoptosis of annulus fibrosus cells; the results were consistent with a previous study on the cytoprotective effects of PF (20).…”

Section: Discussionsupporting

confidence: 81%

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

Chen

Lin

Zheng

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. In the present study, we demonstrate that the degeneration of intervertebral discs is caused by ageing and apoptosis of matrix cells. Apoptosis is as essential as the function of proteoglycan synthesis in assessing the possible degeneration of intervertebral discs; paeoniflorin (PF) induces cytoprotective effects on various types of cells. In this study, the function of PF in inhibiting Fas ligand (FasL)-induced apoptosis in annulus fibrosus cells was assessed, and the correlation between apoptosis and the Fas-FasL pathway was determined. Annulus fibrosus cells were derived from the intervertebral discs of 1-month-old Sprague Dawley rats; the cells were characterised by toluidine blue staining and subjected to apoptosis with FasL. PF was diluted to various concentrations and added to annulus fibrosus cells at various times. The impact of PF and FasL on cell apoptosis of annulus fibrosus cells was determined by flow cytometry. Western blot analysis was performed to determine the protein expression levels of Fas and caspase-3. The percentages of apoptotic annulus fibrosus cells as well as the expression levels of caspase-3 and Fas were significantly reduced following treatment with 208, 20.8 or 2.08 µM PF. PF inhibits the activation of the Fas-FasL signal pathway and decreases FasL-induced apoptosis of annulus fibrosus cells.

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Section: Discussionsupporting

confidence: 81%

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

Chen

Lin

Zheng

et al. 2015

Experimental and Therapeutic Medicine

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“…Studies showed that Fas ligand (FasL), which is an apoptosis inducer and widely expressed in other immune privilege sites, exists in human NP tissues [22,23]. In our previous studies, we found that FasL could induce apoptosis of both vascular endothelial cells and immunocytes including macrophages and CD8 + T cells [24,25]. These studies indicate that FasL might act as a molecular barrier by eliminating blood vessel infiltration and immune cells recruitment.…”

Section: The Blood-np Barriermentioning

confidence: 88%

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Sun¹,

Liu²,

Luo³

2020

Int. J. Med. Sci.

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113

115

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The intervertebral disc (IVD) is the largest avascular organ of the body. It is composed of three parts: the nucleus pulposus (NP), the annulus fibrosus (AF) and the cartilaginous endplate (CEP). The central NP is surrounded by the AF and sandwiched by the two CEPs ever since its formation. This unique structure isolates the NP from the immune system of the host. Additionally, molecular factors expressed in IVD have been shown inhibitive effect on immune cells and cytokines infiltration. Therefore, the IVD has been identified as an immune privilege organ. The steady state of immune privilege is fundamental to the homeostasis of the IVD. The AF and the CEP, along with the immunosuppressive molecular factors are defined as the blood-NP barrier (BNB), which establishes a strong barrier to isolate the NP from the host immune system. When the BNB is damaged, the auto-immune response of the NP occurs with various downstream cascade reactions. This effect plays an important role in the whole process of IVD degeneration and related complications, such as herniation, sciatica and spontaneous herniated NP regression. Taken together, an enhanced understanding of the immune privilege of the IVD could provide new targets for the treatment of symptomatic IVD disease. However, the underlying mechanism above is still not fully clarified. Accordingly, the current study will extensively review and discuss studies regarding the immune privilege of the IVD.

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“…overexpression of VeGF was found in nP cells under inflammatory or degenerated situations, which was considered to be one of the key reasons causing angiogenesis (14). co-culture model also showed that Fas ligand (Fasl) and immune privilege were involved in the process of iVd angiogenesis, indicating a more complicated mechanism of neovascularization of iVds (41,42). TiMP3 was reported as an effective angiogenesis inhibitor in various tumor tissues, which suppressed vascular ingrowth by interfering with the binding of VeGF and VeGFr-2 (15).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus

Pang

Sun

et al. 2020

Mol Med Report

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approximately 50% of the cases of low back pain (lBP) are attributed to discogenic origin. The causes of discogenic pain are complicated and consist of a complex biochemical cascade. neovascularization of intervertebral discs (iVds) is believed to be associated with discogenic pain. The anti-angiogenesis ability of tissue inhibitor of metalloproteinase-3 (TiMP3) has been reported in many tumors, yet whether TiMP3 is associated with neovascularization of iVds remains unknown. in the present study, both in vitro and in vivo models were used to investigate the association between discogenic pain and TiMP3 expression in nucleus pulposus (NP). PCR results demonstrated that inflammation induced downregulation of TiMP3 expression in nP cells. By using an adenovirus system to upregulate TiMP3 expression, the effect of TiMP3 on angiogenesis was measured by endothelial cell migration and tube formation assays. The results demonstrated that overexpression of TiMP3 suppressed angiogenesis in nP without the regulation of vascular endothelial growth factor (VeGF) expression. TnF-α converting enzyme (Tace) expression was downregulated by TiMP3, thus inhibiting the Tace-induced activation of TnF-α in nP cells. Immunohistochemical staining of IVDs also confirmed that TiMP3 inhibited the expression of substance P in nP. Taken together, the present results indicated the expression of TiMP3 in nP may have a key role in the development of discogenic pain.

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FasL Expression on Human Nucleus Pulposus Cells Contributes to the Immune Privilege of Intervertebral Disc by Interacting with Immunocytes

Cited by 33 publications

References 44 publications

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

Protective effects of paeoniflorin against FasL-induced apoptosis of intervertebral disc annulus fibrosus cells via Fas-FasL signalling pathway

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus

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