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Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis

OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subset...

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Autores principales: Cai, Xiao-Yu, Zhu, Yue, Wang, Chen, Tang, Xiao-Yu, Han, Le, Shu, Jin-Ling, Zhang, Xian-Zheng, Liang, Fa-Qin, Ge, Jing-Ru, Xu, Li, Mei, Dan, Zhang, Ling-Ling, Wei, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235293/
https://www.ncbi.nlm.nih.gov/pubmed/32477138
http://dx.doi.org/10.3389/fphar.2020.00676
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author Cai, Xiao-Yu
Zhu, Yue
Wang, Chen
Tang, Xiao-Yu
Han, Le
Shu, Jin-Ling
Zhang, Xian-Zheng
Liang, Fa-Qin
Ge, Jing-Ru
Xu, Li
Mei, Dan
Zhang, Ling-Ling
Wei, Wei
author_facet Cai, Xiao-Yu
Zhu, Yue
Wang, Chen
Tang, Xiao-Yu
Han, Le
Shu, Jin-Ling
Zhang, Xian-Zheng
Liang, Fa-Qin
Ge, Jing-Ru
Xu, Li
Mei, Dan
Zhang, Ling-Ling
Wei, Wei
author_sort Cai, Xiao-Yu
collection PubMed
description OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19(−)CD27(+)CD138(+) plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19(+) total B cells, CD19(+)CD27(+) memory B cells and CD19(−)CD27(+)CD138(+) plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.
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spelling pubmed-72352932020-05-29 Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis Cai, Xiao-Yu Zhu, Yue Wang, Chen Tang, Xiao-Yu Han, Le Shu, Jin-Ling Zhang, Xian-Zheng Liang, Fa-Qin Ge, Jing-Ru Xu, Li Mei, Dan Zhang, Ling-Ling Wei, Wei Front Pharmacol Pharmacology OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19(−)CD27(+)CD138(+) plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19(+) total B cells, CD19(+)CD27(+) memory B cells and CD19(−)CD27(+)CD138(+) plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway. Frontiers Media S.A. 2020-05-12 /pmc/articles/PMC7235293/ /pubmed/32477138 http://dx.doi.org/10.3389/fphar.2020.00676 Text en Copyright © 2020 Cai, Zhu, Wang, Tang, Han, Shu, Zhang, Liang, Ge, Xu, Mei, Zhang and Wei http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cai, Xiao-Yu
Zhu, Yue
Wang, Chen
Tang, Xiao-Yu
Han, Le
Shu, Jin-Ling
Zhang, Xian-Zheng
Liang, Fa-Qin
Ge, Jing-Ru
Xu, Li
Mei, Dan
Zhang, Ling-Ling
Wei, Wei
Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title_full Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title_fullStr Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title_full_unstemmed Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title_short Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis
title_sort etanercept inhibits b cell differentiation by regulating tnfrii/traf2/nf-κb signaling pathway in rheumatoid arthritis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235293/
https://www.ncbi.nlm.nih.gov/pubmed/32477138
http://dx.doi.org/10.3389/fphar.2020.00676
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