title: Adiponectin stimulates prostaglandin E(2) 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-kappaB 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-kappaB activation by adiponectin as well as by interleukin-1beta was observed in RASFs.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Toho University School of Medicine, Ota-ku, Tokyo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kusunoki
authors.forename: Kanako
authors.initials: K
authors.lastname: Kitahara
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kojima
authors.forename: Nahoko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kaichi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Hirahito
authors.initials: H
authors.lastname: Endo
authors.forename: Toru
authors.initials: T
authors.lastname: Suguro
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D053583:Interleukin-1beta; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone