Journal article

Publication year: 2012

Pages: 28378-28385

Journal: Journal of Biological Chemistry

Volume number: 287

Issue number: 34

ISSN: 0021-9258

Open access status: Green

DOI Link: https://doi.org/10.1074/jbc.M111.312884

Publisher: Elsevier

Abstract: 
Adipokines such as adiponectin and visfatin/pre-B-cell colony-enhancing factor (PBEF) have been recently shown to contribute to synovial inflammation in rheumatoid arthritis (RA). In this study, we evaluated the pathophysiological implication of visfatin/PBEF in the molecular patterns of RA synovial tissue, focusing on RA synovial fibroblasts (RASFs), key players in RA synovium. Expression of visfatin/PBEF in synovial fluid and tissue of RA patients was detected by immunoassays and immunohistochemistry. RASFs were stimulated with different concentrations of visfatin/PBEF over varying time intervals, and changes in gene expression were evaluated at the RNA and protein levels using Affymetrix array, real-time PCR, and immunoassays. The signaling pathways involved were identified. The influence of visfatin/PBEF on fibroblast motility and migration was analyzed. In RA synovium, visfatin/PBEF was predominantly expressed in the lining layer, lymphoid aggregates, and interstitial vessels. In RASFs, visfatin/PBEF induced high amounts of chemokines such as IL-8 and MCP-1, proinflammatory cytokines such as IL-6, and matrix metalloproteinases such as MMP-3. Phosphorylation of p38 MAPK was observed after visfatin/PBEF stimulation, and inhibition of p38 MAPK showed strong reduction of visfatin-induced effects. Directed as well as general fibroblast motility was increased by visfatin/PBEF-induced factors. The results of this study indicate that visfatin/PBEF is involved in synovial fibroblast activation by triggering fibroblast motility and promoting cytokine synthesis at central sites in RA synovium.

Harvard Citation style: Meier, F., Frommer, K., Peters, M., Brentano, F., Lefevre, S., Schroeder, D., et al. (2012) Visfatin/Pre-B-cell Colony-enhancing Factor (PBEF), a Proinflammatory and Cell Motility-changing Factor in Rheumatoid Arthritis, Journal of Biological Chemistry, 287(34), pp. 28378-28385. https://doi.org/10.1074/jbc.M111.312884

APA Citation style: Meier, F., Frommer, K., Peters, M., Brentano, F., Lefevre, S., Schroeder, D., Kyburz, D., Steinmeyer, J., Rehart, S., Gay, S., Mueller-Ladner, U., & Neumann, E. (2012). Visfatin/Pre-B-cell Colony-enhancing Factor (PBEF), a Proinflammatory and Cell Motility-changing Factor in Rheumatoid Arthritis. Journal of Biological Chemistry. 287(34), 28378-28385. https://doi.org/10.1074/jbc.M111.312884