IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

Shen, Jieliang; Xu, Shengxi; Zhou, Hao; Liu, Huzhe; Jiang, Wei; Hao, Jie; Hu, Zhenming

doi:10.1038/srep41067

Cited by 77 publications

(57 citation statements)

References 24 publications

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“…Autophagy has been shown to have a positive effect on cell survival by mediating the selective removal of damaged cell components [54,67]. In addition, autophagy has been shown to instigate a protective effect against oxidative damage to endplate chondrocytes in intervertebral discs as the inhibition of autophagy increased apoptosis [68].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

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Section: Discussionmentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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“…S1 A, B ). IL‐1β, also implicated in apoptosis (42), was not affected by sevoflurane. Thus, we sought a different explanation for the attenuation of splenic apoptosis under sevoflurane anesthesia.…”

Section: Resultsmentioning

confidence: 98%

The volatile anesthetic sevoflurane reduces neutrophil apoptosisviaFas death domain–Fas‐associated death domain interaction

Koutsogiannaki

Hou

Babazada³

et al. 2019

FASEB j.

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Sepsis remains a significant health care burden, with high morbidities and mortalities. Patients with sepsis often require general anesthesia for procedures and imaging studies. Knowing that anesthetic drugs can pose immunomodulatory effects, it would be critical to understand the impact of anesthetics on sepsis pathophysiology. The volatile anesthetic sevoflurane is a common general anesthetic derived from ether as a prototype. Using a murine sepsis model induced by cecal ligation and puncture surgery, we examined the impact of sevoflurane on sepsis outcome. Different from volatile anesthetic isoflurane, sevoflurane exposure significantly improved the outcome of septic mice. This was associated with less apoptosis in the spleen. Because splenic apoptosis was largely attributed to the apoptosis of neutrophils, we examined the effect of sevoflurane on FasL‐induced neutrophil apoptosis. Sevoflurane exposure significantly attenuated apoptosis. Sevoflurane did not affect the binding of FasL to the extracellular domain of Fas receptor. Instead, in silico analysis suggested that sevoflurane would bind to the interphase between Fas death domain (DD) and Fas‐associated DD (FADD). The effect of sevoflurane on Fas DD‐FADD interaction was examined using fluorescence resonance energy transfer (FRET). Sevoflurane attenuated FRET efficiency, indicating that sevoflurane hindered the interaction between Fas DD and FADD. The predicted sevoflurane binding site is known to play a significant role in Fas DD‐FADD interaction, supporting our in vitro and in vivo apoptosis results.—Koutsogiannaki, S., Hou, L., Babazada, H., Okuno, T., Blazon‐Brown, N., Soriano, S. G., Yokomizo, T., Yuki, K. The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain‐Fas‐associated death domain interaction. FASEB J. 33, 12668–12679 (2019). http://www.fasebj.org

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“…Anoikis is a form of apoptosis caused specifically by a decrease in the cell adhesion molecules, which leads to reduced cell adhesion and eventually cell death. Caspase‐3, a critical downstream apoptotic protease in the caspase cascade, is not directly suppressed by FAK; however, inhibition of the upstream pathway leads to the activation of caspase‐3 . FAK plays an antiapoptotic role by inhibiting the caspase‐3‐activated apoptotic cascade .…”

Section: Discussionmentioning

confidence: 99%

Fibronectin induced ITGβ1/FAK‐dependent apoptotic pathways determines the fate of degenerative NP cells

Wang

Hua

et al. 2018

Journal Orthopaedic Research

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Intervertebral disc (IVD) degeneration is caused by a decrease in nucleus pulposus (NP) cells, due mainly to apoptosis. Focal adhesion kinase (FAK) is involved in the integrin (ITG)-mediated control of cell adhesion and anoikis (apoptosis). To explore the involvement of ITGb1/FAK-dependent apoptotic pathways in disc degeneration, histological, and molecular biological studies on the protein expression of fibronectin (FN), ITGb1, and syndecan 4 (SYND4) in non-degenerative and degenerative NP tissues were conducted. Degenerative NP cells were isolated and cultured in the presence of SYND4 and/or ITGb1, with or without an FAK inhibitor. The effects of upregulation or knockdown of ITGb1 gene expression were also examined. The TUNEL assay was used to determine the percentage of apoptotic cells. Western blotting was used to detect the expression of SYND4, ITGb1, FAK, and downstream pathway proteins. The results showed that extracellular FN was degraded during the IVD degeneration process, detrimentally affecting the function, and survival of NP cells. The apoptotic rate was increased by ITGb1 activation, but partially reduced by FN. After ITGb1 knockdown, the FAK/PI3 K/AKT axis was activated in the ITGb1/FAK-dependent pathways, resulting in increased cell adherence capacity and decreased anoikis. FN rescued the degenerative NP cells from anoikis through the FAKdependent signaling pathways. In conclusion, the extracellular matrix protein FN is essential for maintaining the function and survival of NP cells through ITGb1/FAK-dependent apoptotic pathways during disc degeneration. ß

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IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

Cited by 77 publications

References 24 publications

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

The volatile anesthetic sevoflurane reduces neutrophil apoptosisviaFas death domain–Fas‐associated death domain interaction

Fibronectin induced ITGβ1/FAK‐dependent apoptotic pathways determines the fate of degenerative NP cells

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