RRC ID |
44445
|
著者 |
Lee GH, Lee J, Lee JW, Choi WS, Moon EY.
|
タイトル |
B cell activating factor-dependent expression of vascular endothelial growth factor in MH7A human synoviocytes stimulated with tumor necrosis factor-α.
|
ジャーナル |
Int Immunopharmacol
|
Abstract |
Angiogenesis in rheumatoid arthritis (RA) is one of the histological hallmarks, which is mediated by expression of vascular endothelial growth factor (VEGF) in RA synovium. VEGF expression is enhanced by TNF-α, the main pro-inflammatory cytokine in RA. B cell activating factor (BAFF) which plays a role in maturation and maintenance of B cells is also associated with autoimmune RA. Here, we investigated whether BAFF could regulate VEGF expression in TNF-α-stimulated synovium using MH7A synovial cells that are established by transfection with the SV40 T antigen. Changes in hBAFF and hVEGF were measured by western blotting, RT-PCR and luciferase promoter assay. When MH7A cells were treated with TNF-α, we observed that TNF-α increased the expression of hBAFF and hVEGF. TNF-α also increased transcriptional activity of hBAFF and hVEGF as judged by luciferase promoter assay. Inhibition of hBAFF expression with BAFF-siRNA decreased transcriptional level and activity of hVEGF. In addition, when c-fos expression was inhibited by the transfection of MH7A cells with c-fos-siRNA, data showed that transcriptional level and activity of both hBAFF and hVEGF were attenuated by the activation with TNF-α. Our results demonstrate for the first time that VEGF-mediated angiogenesis in RA could be controlled by TNF-α-induced BAFF expression through c-Fos. Data suggest that TNF-α-induced BAFF expression and BAFF-mediated VEGF expression in synovium may cooperate to maintain the capacity of such cells to protect B cells from apoptosis and the supply of nutrients and oxygen in inflammatory microenvironments.
|
巻・号 |
17(1)
|
ページ |
142-7
|
公開日 |
2013-9-1
|
DOI |
10.1016/j.intimp.2013.04.026
|
PII |
S1567-5769(13)00172-0
|
PMID |
23684916
|
MeSH |
Arthritis, Rheumatoid / metabolism
Arthritis, Rheumatoid / pathology
B-Cell Activating Factor / genetics
B-Cell Activating Factor / metabolism*
Cell Line
Dose-Response Relationship, Drug
Humans
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogene Proteins c-fos / metabolism
RNA Interference
Synovial Membrane / cytology*
Tumor Necrosis Factor-alpha / pharmacology*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism*
|
IF |
3.943
|
引用数 |
15
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
IMMUNOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MH7A(RCB1512) |