RRC ID 44445
Author Lee GH, Lee J, Lee JW, Choi WS, Moon EY.
Title B cell activating factor-dependent expression of vascular endothelial growth factor in MH7A human synoviocytes stimulated with tumor necrosis factor-α.
Journal 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.
Volume 17(1)
Pages 142-7
Published 2013-9
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 3.361
Times Cited 6
Human and Animal Cells