Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis
Version of Record online: 18 JUN 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 10, pages 2886–2899, October 2010
How to Cite
Frommer, K. W., Zimmermann, B., Meier, F. M. P., Schröder, D., Heil, M., Schäffler, A., Büchler, C., Steinmeyer, J., Brentano, F., Gay, S., Müller-Ladner, U. and Neumann, E. (2010), Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis & Rheumatism, 62: 2886–2899. doi: 10.1002/art.27616
- Issue online: 18 JUN 2010
- Version of Record online: 18 JUN 2010
- Accepted manuscript online: 18 JUN 2010 12:00AM EST
- Manuscript Accepted: 10 JUN 2010
- Manuscript Received: 23 JUL 2009
- German Research Foundation (DFG research grant). Grant Number: NE1174/3-1
- European Community Sixth Framework Programme Autocure
- European Community Seventh Framework Programme Masterswitch
- Institute of Arthritis Research Epalinges
Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells.
Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription–polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors.
Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent.
Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion.