Adiponectin stimulates prostaglandin E₂ production in rheumatoid arthritis synovial fibroblasts

Abstract

Objective. Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E 2 (PGE 2 ) by rheumatoid arthritis synovial fibroblasts (RASFs).Methods. Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. Fibroblast-like cells from the third or fourth passage were used as RASFs. Expression of adiponectin receptor messenger RNA (mRNA) and protein was detected. PGE 2 (converted from arachidonic acid) was measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA and protein for cyclooxygenase 2 (COX-2) and membrane-associated PGE synthase 1 (mPGES-1), key enzymes involved in PGE 2 synthesis, was detected in RASFs. The effects of RNA interference (RNAi) targeting the adiponectin receptor genes and the receptor signal inhibitors were examined. The influence of adiponectin on NF-B activation in RASFs was measured with an ELISA kit.Results. Adiponectin receptors were detected in RASFs. Adiponectin increased both COX-2 and mPGES-1 mRNA and protein expression by RASFs in a time-and concentration-dependent manner. PGE 2 production by RASFs was also increased by the addition of adiponectin, and this increase was inhibited by RNAi for the adiponectin receptor gene, or coincubation with the receptor signal inhibitors. Enhancement of NF-B activation by adiponectin as well as by interleukin-1␤ was observed in RASFs.Conclusion. Our findings indicate that adiponectin induces COX-2 and mPGES-1 expression, resulting in the enhancement of PGE 2 production by RASFs. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients.

Serum adipokine profiles in Kawasaki disease

“…It was also shown that adiponectin stimulates the production of interleukin-8 [29] and prostaglandin E 2 [30] by rheumatoid synovial fibroblasts, suggesting that adiponectin might act as a proinflammatory cytokine in rheumatoid inflammation. Adiponectin is secreted by not only adipocytes, but also in synovial fibroblasts in patients with rheumatoid arthritis [31].…”

Protective role of adiponectin against ethanol-induced gastric injury in mice

“…Collectively, the present in vitro findings suggest that adiponectin protects the gastric mucosa from ethanol-induced injury, partially through activation of the COX-2/PGE 2 pathway in gastric epithelial cells. Kusunoki et al (18) showed that adiponectin-induced PGE 2 production is mediated partially by adiponectin receptors, AdipoR1 and AdipoR2 in rheumatoid arthritis synovial fibroblasts. Lee et al (22) showed that adiponectin activates AdipoR1 to increase the expression of COX-2 in mesenchymal progenitor cells.…”

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

“…Adiponectin stimulates PGE 2 and IL-8 production in RA synovial fibroblast (93,94). In addition, it was also reported in RA synovial fibroblast that adiponectin is able to stimulate the production of IL-6, PGE 2 , vascular endothelial growth factor, and MMP-1 and MMP-13 (43,95).…”