PMID- 20222108
OWN - NLM
STAT- MEDLINE
DCOM- 20100628
LR  - 20220330
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 62
IP  - 6
DP  - 2010 Jun
TI  - Adiponectin stimulates prostaglandin E(2) production in rheumatoid arthritis 
      synovial fibroblasts.
PG  - 1641-9
LID - 10.1002/art.27450 [doi]
AB  - 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. 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.
FAU - Kusunoki, Natsuko
AU  - Kusunoki N
AD  - Toho University School of Medicine, Ota-ku, Tokyo, Japan.
FAU - Kitahara, Kanako
AU  - Kitahara K
FAU - Kojima, Fumiaki
AU  - Kojima F
FAU - Tanaka, Nahoko
AU  - Tanaka N
FAU - Kaneko, Kaichi
AU  - Kaneko K
FAU - Endo, Hirahito
AU  - Endo H
FAU - Suguro, Toru
AU  - Suguro T
FAU - Kawai, Shinichi
AU  - Kawai S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Adiponectin)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Adiponectin)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.99.3 (PTGES protein, human)
RN  - EC 5.3.99.3 (Prostaglandin-E Synthases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adiponectin/genetics/*metabolism/pharmacology
MH  - Arthritis, Rheumatoid/genetics/*metabolism
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Dinoprostone/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/cytology/drug effects/*metabolism
MH  - Humans
MH  - Interleukin-1beta/metabolism/pharmacology
MH  - Intramolecular Oxidoreductases/genetics/metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Prostaglandin-E Synthases
MH  - RNA Interference
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Adiponectin/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/genetics
MH  - Synovial Membrane/cytology/drug effects/*metabolism
EDAT- 2010/03/12 06:00
MHDA- 2010/06/29 06:00
CRDT- 2010/03/12 06:00
PHST- 2010/03/12 06:00 [entrez]
PHST- 2010/03/12 06:00 [pubmed]
PHST- 2010/06/29 06:00 [medline]
AID - 10.1002/art.27450 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2010 Jun;62(6):1641-9. doi: 10.1002/art.27450.