Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes.
Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volun...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3428310?pdf=render |
| _version_ | 1818470727419953152 |
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| author | Wen Zhang Qun Shi Xiaotian Xu Hua Chen Wei Lin Fengchun Zhang Xiaofeng Zeng Xuan Zhang Denian Ba Wei He |
| author_facet | Wen Zhang Qun Shi Xiaotian Xu Hua Chen Wei Lin Fengchun Zhang Xiaofeng Zeng Xuan Zhang Denian Ba Wei He |
| author_sort | Wen Zhang |
| collection | DOAJ |
| description | Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. Results showed CD40-induced NF-κB signaling was constitutively activated in B cells from active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IκBα, phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further phosphorylation and degradation of IκBα, as well as phosphorylation of P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of tonsil B cells, in that IKKα/β were more activated compared to normal B cells. CD40-induced NF-κB activity was blocked by both IκB phosphorylation and proteosome degradation inhibitors in both lupus and normal B cells. All together, our findings revealed that canonical NF-κB signaling is constitutively activated in active lupus and is mediated by CD154/CD40. CD40 induced NF-κB activation is different in human lupus B lymphocytes compared with normal B cells. |
| first_indexed | 2024-04-13T21:42:06Z |
| format | Article |
| id | doaj.art-e5635ed6197b47fd8c354c63bc9a0d23 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T21:42:06Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e5635ed6197b47fd8c354c63bc9a0d232022-12-22T02:28:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4164410.1371/journal.pone.0041644Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes.Wen ZhangQun ShiXiaotian XuHua ChenWei LinFengchun ZhangXiaofeng ZengXuan ZhangDenian BaWei HeAuto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. Results showed CD40-induced NF-κB signaling was constitutively activated in B cells from active lupus patients, including decreased CD40 in raft portion, increased phosphorylation and degradation of IκBα, phosphorylation of P65, as well as increased nuclear translocation of P65, P50, c-Rel, which could be blocked by anti-CD154. CD154 stimulation could induce further phosphorylation and degradation of IκBα, as well as phosphorylation of P65 and nuclear translocation of P65. In addition, CD40-induced kinase activities in B cells from lupus patients mimicked that of tonsil B cells, in that IKKα/β were more activated compared to normal B cells. CD40-induced NF-κB activity was blocked by both IκB phosphorylation and proteosome degradation inhibitors in both lupus and normal B cells. All together, our findings revealed that canonical NF-κB signaling is constitutively activated in active lupus and is mediated by CD154/CD40. CD40 induced NF-κB activation is different in human lupus B lymphocytes compared with normal B cells.http://europepmc.org/articles/PMC3428310?pdf=render |
| spellingShingle | Wen Zhang Qun Shi Xiaotian Xu Hua Chen Wei Lin Fengchun Zhang Xiaofeng Zeng Xuan Zhang Denian Ba Wei He Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. PLoS ONE |
| title | Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. |
| title_full | Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. |
| title_fullStr | Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. |
| title_full_unstemmed | Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. |
| title_short | Aberrant CD40-induced NF-κB activation in human lupus B lymphocytes. |
| title_sort | aberrant cd40 induced nf κb activation in human lupus b lymphocytes |
| url | http://europepmc.org/articles/PMC3428310?pdf=render |
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