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Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes

INTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor α (TNF-α) as this has proven benefits. However, a large number of patients do not respond to or become resistant to anti...

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Autores principales: Buhrmann, Constanze, Shayan, Parviz, Aggarwal, Bharat B, Shakibaei, Mehdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979010/
https://www.ncbi.nlm.nih.gov/pubmed/24283517
http://dx.doi.org/10.1186/ar4393
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author Buhrmann, Constanze
Shayan, Parviz
Aggarwal, Bharat B
Shakibaei, Mehdi
author_facet Buhrmann, Constanze
Shayan, Parviz
Aggarwal, Bharat B
Shakibaei, Mehdi
author_sort Buhrmann, Constanze
collection PubMed
description INTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor α (TNF-α) as this has proven benefits. However, a large number of patients do not respond to or become resistant to anti-TNF-α therapy. While the role of TNF-α in RA is quite evident, the role of TNF-β, also called lymphotoxin-α (LT-α), is unclear. In this study we investigated whether TNF-β and its receptor play a role in chondrocytes in the inflammatory environment. METHODS: An in vitro model of primary human chondrocytes was used to study TNF-β-mediated inflammatory signaling. RESULTS: Cytokine-induced inflammation enhances TNF-β and TNF-β-receptor expression in primary human chondrocytes accompanied by the up-regulation of inflammatory (cyclooxygenase-2), matrix degrading (matrix metalloproteinase-9 and -13) and apoptotic (p53, cleaved caspase-3) signaling pathways, all known to be regulated by NF-κB. In contrast, anti-TNF-β, similar to the natural NF-κB inhibitor (curcumin, diferuloylmethane) or the knockdown of NF-κB by using antisense oligonucleotides (ASO), suppressed IL-1β-induced NF-κB activation and its translocation to the nucleus, and abolished the pro-inflammatory and apoptotic effects of IL-1β. This highlights, at least in part, the crucial role of NF-κB in TNF-β-induced-inflammation in cartilage, similar to that expected for TNF-α. Finally, the adhesiveness between TNF-β-expressing T-lymphocytes and the responding chondrocytes was significantly enhanced through a TNF-β-induced inflammatory microenvironment. CONCLUSIONS: These results suggest for the first time that TNF-β is involved in microenvironment inflammation in chondrocytes during RA parallel to TNF-α, resulting in the up-regulation of NF-κB signaling and activation of pro-inflammatory activity.
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spelling pubmed-39790102014-04-09 Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes Buhrmann, Constanze Shayan, Parviz Aggarwal, Bharat B Shakibaei, Mehdi Arthritis Res Ther Research Article INTRODUCTION: Inflammatory cytokines play a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Current therapies target mainly tumor necrosis factor α (TNF-α) as this has proven benefits. However, a large number of patients do not respond to or become resistant to anti-TNF-α therapy. While the role of TNF-α in RA is quite evident, the role of TNF-β, also called lymphotoxin-α (LT-α), is unclear. In this study we investigated whether TNF-β and its receptor play a role in chondrocytes in the inflammatory environment. METHODS: An in vitro model of primary human chondrocytes was used to study TNF-β-mediated inflammatory signaling. RESULTS: Cytokine-induced inflammation enhances TNF-β and TNF-β-receptor expression in primary human chondrocytes accompanied by the up-regulation of inflammatory (cyclooxygenase-2), matrix degrading (matrix metalloproteinase-9 and -13) and apoptotic (p53, cleaved caspase-3) signaling pathways, all known to be regulated by NF-κB. In contrast, anti-TNF-β, similar to the natural NF-κB inhibitor (curcumin, diferuloylmethane) or the knockdown of NF-κB by using antisense oligonucleotides (ASO), suppressed IL-1β-induced NF-κB activation and its translocation to the nucleus, and abolished the pro-inflammatory and apoptotic effects of IL-1β. This highlights, at least in part, the crucial role of NF-κB in TNF-β-induced-inflammation in cartilage, similar to that expected for TNF-α. Finally, the adhesiveness between TNF-β-expressing T-lymphocytes and the responding chondrocytes was significantly enhanced through a TNF-β-induced inflammatory microenvironment. CONCLUSIONS: These results suggest for the first time that TNF-β is involved in microenvironment inflammation in chondrocytes during RA parallel to TNF-α, resulting in the up-regulation of NF-κB signaling and activation of pro-inflammatory activity. BioMed Central 2013 2013-11-28 /pmc/articles/PMC3979010/ /pubmed/24283517 http://dx.doi.org/10.1186/ar4393 Text en Copyright © 2013 Buhrmann et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Buhrmann, Constanze
Shayan, Parviz
Aggarwal, Bharat B
Shakibaei, Mehdi
Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title_full Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title_fullStr Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title_full_unstemmed Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title_short Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
title_sort evidence that tnf-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979010/
https://www.ncbi.nlm.nih.gov/pubmed/24283517
http://dx.doi.org/10.1186/ar4393
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