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B Cell Adhesion to Fibroblast-Like Synoviocytes Is Up-Regulated by Tumor Necrosis Factor-Alpha via Expression of Human Vascular Cell Adhesion Molecule-1 Mediated by B Cell-Activating Factor
Fibroblast-like synoviocytes (FLSs) play a key role in the pathogenesis of rheumatoid arthritis (RA) by producing inflammatory cytokines and interacting with various immune cells, which contribute to cartilage destruction. RA-FLSs activated by tumor necrosis factor alpha (TNF-α), exacerbate joint da...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267633/ https://www.ncbi.nlm.nih.gov/pubmed/34281218 http://dx.doi.org/10.3390/ijms22137166 |
Sumario: | Fibroblast-like synoviocytes (FLSs) play a key role in the pathogenesis of rheumatoid arthritis (RA) by producing inflammatory cytokines and interacting with various immune cells, which contribute to cartilage destruction. RA-FLSs activated by tumor necrosis factor alpha (TNF-α), exacerbate joint damage by triggering the expression of various inflammatory molecules, including human vascular cell adhesion molecule-1 (hVCAM1) and B cell-activating factor (hBAFF), with a role in maturation and maintenance of B cells. Here, we investigated whether B cell interaction with FLSs could be associated with hVCAM1 expression by TNF-α through hBAFF, using WiL2-NS B cells and MH7A synovial cells. TNF-α enhanced the expression of hVCAM1 and hBAFF. B cell adhesion to FLSs was increased by treatment with TNF-α or hBAFF protein. hVCAM expression was up-regulated by transcriptional activation of the hVCAM1 promoter(−1549 to −54) in MH7A cells treated with hBAFF protein or overexpressed with hBAFF gene. In contrast, hVCAM1 expression was down-regulated by treatment with hBAFF-siRNA. JNK was activated by TNF-α treatment. Then, hVCAM1 expression and B cell adhesion to FLSs were reduced by the treatment with JNK inhibitor SP600125. Transcriptional activity of hVCAM1 by the stimulation with TNF-α was inhibited by the deletion of −1549 to −229 from the hVCAM1 promoter. hVCAM1 expression and B cell adhesion to FLSs were reduced by treatment with hVCAM1-siRNA. Taken together, these results suggest that B cell adhesion to FLSs is associated with TNF-α-induced up-regulation of hVCAM1 expression via hBAFF expression. Thus, the pathological progression of RA may be associated with hVCAM1-mediated interaction of synovial cells with B lymphocytes. |
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