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Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway

AIMS: Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate signi...

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Autores principales: Lou, Aiju, Wang, Le, Lai, Weinan, Zhu, DingJi, Wu, Weirong, Wang, Zhao, Cai, Zihong, Yang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The British Editorial Society of Bone & Joint Surgery 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077182/
https://www.ncbi.nlm.nih.gov/pubmed/33827262
http://dx.doi.org/10.1302/2046-3758.104.BJR-2020-0085.R2
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author Lou, Aiju
Wang, Le
Lai, Weinan
Zhu, DingJi
Wu, Weirong
Wang, Zhao
Cai, Zihong
Yang, Min
author_facet Lou, Aiju
Wang, Le
Lai, Weinan
Zhu, DingJi
Wu, Weirong
Wang, Zhao
Cai, Zihong
Yang, Min
author_sort Lou, Aiju
collection PubMed
description AIMS: Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. METHODS: We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. RESULTS: AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. CONCLUSION: The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE–NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259–268.
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spelling pubmed-80771822021-05-04 Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway Lou, Aiju Wang, Le Lai, Weinan Zhu, DingJi Wu, Weirong Wang, Zhao Cai, Zihong Yang, Min Bone Joint Res Synovium AIMS: Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. METHODS: We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. RESULTS: AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. CONCLUSION: The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE–NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259–268. The British Editorial Society of Bone & Joint Surgery 2021-04-01 /pmc/articles/PMC8077182/ /pubmed/33827262 http://dx.doi.org/10.1302/2046-3758.104.BJR-2020-0085.R2 Text en © 2021 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Synovium
Lou, Aiju
Wang, Le
Lai, Weinan
Zhu, DingJi
Wu, Weirong
Wang, Zhao
Cai, Zihong
Yang, Min
Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title_full Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title_fullStr Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title_full_unstemmed Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title_short Advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the RAGE-NF-κB pathway
title_sort advanced oxidation protein products induce inflammatory responses and invasive behaviour in fibroblast-like synoviocytes via the rage-nf-κb pathway
topic Synovium
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077182/
https://www.ncbi.nlm.nih.gov/pubmed/33827262
http://dx.doi.org/10.1302/2046-3758.104.BJR-2020-0085.R2
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