Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

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.

The effect of multimeric adiponectin isoforms and leptin on the function of rheumatoid fibroblast-like synoviocytes

“…This discrepancy may result from the application in our experiments of adiponectin isoforms instead of native adiponectin and higher, but still physiologically relevant, concentrations of IL-1β. Although the synergistic effect was associated with the up-regulation of FLS receptors for IL-1 and adiponectin, no synergy in the production of MMPs was observed (13). The latter observation is consistent with the results of our current study (Figure 2).…”

“…In vitro data suggest that adiponectin contributes to joint inflammation and destruction. Some reports have demonstrated that, at a concentration of 10 μg/mL, adiponectin increases the production of pro-inflammatory cytokines, chemokines, growth factors, and MMPs to levels lower than (IL-6, IL-8) or similar to (MMP-1, MMP-13, VEGF) the level triggered by 0.1-10 ng/mL of IL-1β (12,13). Moreover, at a very high (25 μg/mL) concentration, adiponectin was reported to up-regulate the expression of numerous genes/proteins relevant to RA pathogenesis (e.g.…”

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

“…For example, IL-1b was reported to be a potent inducer of other cytokines, including IL-8 or CCL2. [40][41][42] We found glomerular monocyte accumulation, significantly elevated renal IL-1b levels, and pharmacological IL-1 receptor blockade that protected Phox-deficient mice from NCGN, making Phoxdysregulated IL-1b generation an attractive candidate mechanism for disease acceleration. In the presence of ANCA, Phox deficiency caused accelerated monocyte caspase-1 activity and increased IL-1b generation in vitro.…”

Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways

“…Briefly, BV2 cells (1 × 10 5 cells/mL) were plated in 24-well plates and pre-treated with the indicated concentrations of anthocyanins for 1 h before treatment with 0.5 μg/mL LPS for 24 h. One hundred microliters of culture-medium supernatants was collected to determine IL-1β, and TNF-α concentrations by ELISA [45]. …”