Adiponectin‐mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis

Abstract

Objective. 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.Methods. 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 transcriptionpolymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors.Results

Adipocytokines as driving forces in rheumatoid arthritis and related inflammatory diseases?

“…However, this stimulatory capacity of adiponectin is not restricted to RASFs. In endothelial cells, chondrocytes and lymphocyte subpopulations, proinflammatory factors, and chemokines were also induced by adiponectin (36). Additionally, adiponectin increased the expression of MMPs in chondrocytes and that of adhesion molecules in endothelial cells (36).…”

“…In endothelial cells, chondrocytes and lymphocyte subpopulations, proinflammatory factors, and chemokines were also induced by adiponectin (36). Additionally, adiponectin increased the expression of MMPs in chondrocytes and that of adhesion molecules in endothelial cells (36). Thus, adiponectin exerts proinflammatory and prodestructive properties in the majority of cells involved in cartilage destruction in RA.…”

“…When stimulated with adiponectin, synovial fibroblasts (SFs), the central cells of cartilage destruction in RA, secrete increased amounts of proinflammatory cytokines such as IL-6, a variety of chemokines including IL-8 and growth-related oncogene ␣, proangiogenic factors such as vascular endothelial growth factor (VEGF), and matrix-degrading proteins including matrix metalloproteinase 1 (MMP-1) and MMP-13 (26,(33)(34)(35)(36). Of note, adiponectin serum levels in patients with RA but not in patients with OA correlate with VEGF levels (33).…”

“…In OA synovial tissue, adiponectin is present in the lining layer and around vessels (26). Adiponectin is, to some extent, also able to induce proinflammatory factors, chemokines, and MMPs in SFs from patients with OA (36).…”

Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines

“…It promotes inflammation through increased TNF␣, IL-6, IL-8, and RANTES secretion by human primary lymphocytes. Likewise, it induces IL-6, IL-8, growth-related oncogene ␣, MCP-1, and RANTES secretion by human macrovascular endothelial cells (97). On the contrary, Lee et al have reported in mice that adiponectin mitigates the severity of collagen-induced arthritis (98).…”