Cargando…

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

Background: 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. Objective: To investigate the protective role of TGF-β1 against TN...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Jingjing, Li, Bo, Yao, Bing, Zhang, Pingchao, Wang, Lixin, Lu, Hua, Song, Xuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005578/
https://www.ncbi.nlm.nih.gov/pubmed/31808511
http://dx.doi.org/10.1042/BSR20191726
_version_ 1783494966267346944
author Xie, Jingjing
Li, Bo
Yao, Bing
Zhang, Pingchao
Wang, Lixin
Lu, Hua
Song, Xuan
author_facet Xie, Jingjing
Li, Bo
Yao, Bing
Zhang, Pingchao
Wang, Lixin
Lu, Hua
Song, Xuan
author_sort Xie, Jingjing
collection PubMed
description Background: 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. Objective: To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism. Methods: Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investigate its protective effects against TNF-α-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-α-treated NP cells, TGF-β1 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-β1 in NP cells treated with TNF-α. Additionally, expression of Fas and FasL in TNF-α-treated NP cells partly decreased by TGF-β1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-β1 and TNF-α. Conclusion: TGF-β1 helps to inhibit TNF-α-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-β1 may be effective to retard inflammation-mediated disc degeneration.
format Online
Article
Text
id pubmed-7005578
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-70055782020-02-13 Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment Xie, Jingjing Li, Bo Yao, Bing Zhang, Pingchao Wang, Lixin Lu, Hua Song, Xuan Biosci Rep Aging Background: 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. Objective: To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism. Methods: Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investigate its protective effects against TNF-α-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-α-treated NP cells, TGF-β1 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-β1 in NP cells treated with TNF-α. Additionally, expression of Fas and FasL in TNF-α-treated NP cells partly decreased by TGF-β1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-β1 and TNF-α. Conclusion: TGF-β1 helps to inhibit TNF-α-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-β1 may be effective to retard inflammation-mediated disc degeneration. Portland Press Ltd. 2020-02-04 /pmc/articles/PMC7005578/ /pubmed/31808511 http://dx.doi.org/10.1042/BSR20191726 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Aging
Xie, Jingjing
Li, Bo
Yao, Bing
Zhang, Pingchao
Wang, Lixin
Lu, Hua
Song, Xuan
Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title_full Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title_fullStr Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title_full_unstemmed Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title_short Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
title_sort transforming growth factor-β1-regulated fas/fasl pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005578/
https://www.ncbi.nlm.nih.gov/pubmed/31808511
http://dx.doi.org/10.1042/BSR20191726
work_keys_str_mv AT xiejingjing transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT libo transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT yaobing transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT zhangpingchao transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT wanglixin transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT luhua transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment
AT songxuan transforminggrowthfactorb1regulatedfasfaslpathwayactivationsuppressesnucleuspulposuscellapoptosisinaninflammatoryenvironment