Rheumatoid Arthritis Basic Science Studies
Adiponectin stimulates prostaglandin E2 production in rheumatoid arthritis synovial fibroblasts
Article first published online: 10 MAR 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 6, pages 1641–1649, June 2010
How to Cite
Kusunoki, N., Kitahara, K., Kojima, F., Tanaka, N., Kaneko, K., Endo, H., Suguro, T. and Kawai, S. (2010), Adiponectin stimulates prostaglandin E2 production in rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism, 62: 1641–1649. doi: 10.1002/art.27450
- Issue published online: 28 MAY 2010
- Article first published online: 10 MAR 2010
- Accepted manuscript online: 10 MAR 2010 12:00AM EST
- Manuscript Accepted: 25 FEB 2010
- Manuscript Received: 6 JUN 2009
- Japanese Ministry of Education, Culture, Sports, Science, and Technology. Grant Number: 17590477
- Ministry of Health, Labor, and Welfare of Japan
- Toho University Graduate School of Medicine. Grant Number: Research Promotion grant 07-04
Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E2 (PGE2) by rheumatoid arthritis synovial fibroblasts (RASFs).
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. PGE2 (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 PGE2 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.
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. PGE2 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.
Our findings indicate that adiponectin induces COX-2 and mPGES-1 expression, resulting in the enhancement of PGE2 production by RASFs. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients.