Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783535934316216320 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7235293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT caixiaoyu etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT zhuyue etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT wangchen etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT tangxiaoyu etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT hanle etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT shujinling etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT zhangxianzheng etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT liangfaqin etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT gejingru etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT xuli etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT meidan etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT zhanglingling etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis AT weiwei etanerceptinhibitsbcelldifferentiationbyregulatingtnfriitraf2nfkbsignalingpathwayinrheumatoidarthritis |