Abstract
To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
Highlights
Adipose tissue, which once was recognized as a lipid storage and release depot, is considered an endocrine tissue (Ronti et al, 2006; Halberg et al, 2008)
Synergistic effect of adiponectin on the production of IL-6, IL-8, and prostaglandin E2 (PGE2) in IL-1β-stimulated rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) To evaluate the synergistic effects of adiponectin and IL-1β on inflammation and joint destruction in arthritic joints, cultured synovial cells were treated with IL-1β (10 or 100 pg/ml) and adiponectin (10 μg/ml) for 24 h
When synovial cells were stimulated with adiponectin and IL-1β at the same time, the protein expression of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs)-1, and MMP-13 was not synergistically stimulated by the two cytokines in RA FLSs
Summary
Adipose tissue, which once was recognized as a lipid storage and release depot, is considered an endocrine tissue (Ronti et al, 2006; Halberg et al, 2008). This tissue secretes various substances (known as adipokines), including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, leptin, adiponectin, resistin, visfatin, omenetin, and many others (Matsuzawa et al, 1999; Henry and Clarke, 2008). Adiponectin has demonstrated beneficial effects against the development of obesity-related vascular diseases (Giannessi et al, 2007), and stimulates angiogenesis (Ribatti et al, 2007)
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