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