ABSTRACT
Adiponectin is an adipokine that modulates insulin sensitivity and has an antiatherosclerotic eff ect. It has also been reported to show an association with rheumatoid arthritis (RA), which is a chronic systemic infl ammatory disease. It was reported that the serum/plasma concentration of adiponectin is higher in patients with RA than in healthy controls or patients with osteoarthritis (OA). In the synovial fl uid of RA patients, the adiponectin level is also higher than in fl uid from OA patient. Th ese reports suggest that adiponectin might contribute to the pathogenesis of arthritis. Because synovial fi broblasts are a major source of infl ammation in RA, the possible eff ect of adiponectin on these cells has been investigated. It was reported that adiponectin stimulates production of interleukin (IL)-6, a very important pro-infl ammatory cytokine for RA, by rheumatoid synovial fi broblasts (RSF). Th is action was related to activation of 5’-adenosine monophosphate-activated protein kinase (AMPK), p38 MAP kinase, and nuclear factor-κB (NF-κB). We found that adiponectin enhanced the production of a chemokine, IL-8, by RSF. Th ese fi ndings suggest that adiponectin may trigger the excessive immune response in RA. Furthermore, adiponectin induces the production of prostaglandin E2 by RSF via up-regulation of the expression of cyclooxygenase-2 and membrane-associated prostaglandin E synthase-1. Th is eff ect of adiponectin might arise from activation of the nuclear translocation of
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NF-κB. Moreover, increased production of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) by RSF and/or chondrocytes were reported. Th erefore, it is possible that adiponectin regulates not only synovial infl ammation, but also joint destruction in RA patients, suggesting that it may have important pathophysiological eff ects on RA joints.
