Open AccessAdiponectin stimulates prostaglandin E 2 production in rheumatoid arthritis synovial fibroblasts
Author(s) -
Kusunoki Natsuko,
Kitahara Kanako,
Kojima Fumiaki,
Tanaka Nahoko,
Kaneko Kaichi,
Endo Hirahito,
Suguro Toru,
Kawai Shinichi
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27450
Subject(s) - adiponectin , adiponectin receptor 1 , medicine , endocrinology , receptor , cyclooxygenase , prostaglandin , adipokine , prostaglandin e , inflammation , chemistry , messenger rna , biology , enzyme , biochemistry , insulin , gene , insulin resistance
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‐κB 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‐κB activation by adiponectin as well as by interleukin‐1β 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.