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Transforming growth factor-?1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment.

ABSTRACT: BACKGROUND:During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-? is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-?1 has the potential to regenerate degenerative disc. OBJECTIVE:To investigate the protective role of TGF-?1 against TNF-?-mediated NP cell apoptosis and the underlying mechanism. METHODS:Rat NP cells were treated with TNF-? (100 ng/ml) for 48 h. TGF-?1 was added into the culture medium to investigate its protective effects against TNF-?-induced NP cell apoptosis. Exogenous FasL was used to investigate the potential role of the Fas/FasL pathway in this process. Flow cytometry assay was used to analyze NP cell apoptosis. Real-time PCR and Western blotting were used to analyze gene and protein expression of apoptosis-related molecules. RESULTS:In TNF-?-treated NP cells, TGF-?1 significantly decreased NP cell apoptosis, declined caspase-3 and -8 activity, and decreased expression of Bax and caspase-3 (cleaved-caspase-3) but increased expression of Bcl-2. However, exogenous FasL partly reversed these effects of TGF-?1 in NP cells treated with TNF-?. Additionally, expression of Fas and FasL in TNF-?-treated NP cells partly decreased by TGF-?1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-?1 and TNF-?. CONCLUSION:TGF-?1 helps to inhibit TNF-?-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-?1 may be effective to retard inflammation-mediated disc degeneration.

SUBMITTER: Xie J

PROVIDER: S-EPMC7005578 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment.

Xie Jingjing J Li Bo B Yao Bing B Zhang Pingchao P Wang Lixin L Lu Hua H Song Xuan X

Bioscience reports 20200201 2

<h4>Background</h4>During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-α is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-β1 has the potential to regenerate degenerative disc.<h4>Objective</h4>To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism.<h4>Methods</h4>Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investig ...[more]

PMID: 31808511

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Project description:Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence β-galactosidase staining was used to detect the activity levels of β-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1β and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.

Dataset Information

Transforming growth factor-?1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment.

Publications

Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment.

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