PMID- 15868626
OWN - NLM
STAT- MEDLINE
DCOM- 20050809
LR  - 20161124
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 32
IP  - 5
DP  - 2005 May
TI  - Expression and regulation of microsomal prostaglandin E synthase-1 in human 
      osteoarthritic cartilage and chondrocytes.
PG  - 887-95
AB  - OBJECTIVE: Elevated production of prostaglandin E2 (PGE2) plays an important role 
      in the pathogenesis of arthritis. Recently, an inducible microsomal prostaglandin 
      E synthase-1 (mPGES-1) was identified. This enzyme is functionally coupled with 
      cyclooxygenase-2 (COX-2) and converts the COX product PGH2 to PGE2. We analyzed 
      expression of mPGES-1 in human normal and osteoarthritic (OA) cartilage and 
      determined the effect of different inflammatory agonists on the expression of 
      mPGES-1 in OA chondrocytes. METHODS: Expression of mPGES-1 mRNA and protein in 
      cartilage was determined by quantitative real-time reverse 
      transcriptase-polymerase chain reaction and immunohistochemistry, respectively. 
      OA chondrocytes were treated with different inflammatory agents, and mPGES-1 
      protein expression was evaluated by Western blot. Activation of the mPGES-1 
      promoter was assessed in transient transfection experiments. RESULTS: Levels of 
      mPGES-1 mRNA and protein were markedly elevated in OA versus normal cartilage. 
      Treatment of chondrocytes with interleukin 1beta (IL-1beta) induced expression of 
      mPGES-1 protein in a dose- and time-dependent manner. This appears to occur at 
      the transcriptional level, as IL-1beta induced expression of mPGES-1 mRNA and the 
      activity of this gene promoter. Tumor necrosis factor-alpha (TNF-alpha) and IL-17 
      also upregulated expression of mPGES-1 protein and displayed a synergistic effect 
      with IL-1beta. Peroxisome proliferator-activated receptor-gamma ligands, 
      15-deoxy-delta(12,14)-prostaglandin J2 and troglitazone, inhibited 
      IL-1beta-induced mPGES-1 protein expression, an effect that was reversed by 
      exogenous PGE2. CONCLUSION: Our study shows that mPGES-1 expression is 
      upregulated in OA versus normal cartilage and that proinflammatory cytokines 
      increased mPGES-1 expression in chondrocytes. These data suggest that mPGES-1 may 
      prove to be an interesting therapeutic target for controlling PGE2 synthesis.
FAU - Li, Xinfang
AU  - Li X
AD  - Osteoarthritis Research Unit, Centre hospitalier de l'Universite de Montreal, 
      Hopital Notre-Dame, Montreal, Quebec, Canada.
FAU - Afif, Hassan
AU  - Afif H
FAU - Cheng, Saranette
AU  - Cheng S
FAU - Martel-Pelletier, Johanne
AU  - Martel-Pelletier J
FAU - Pelletier, Jean-Pierre
AU  - Pelletier JP
FAU - Ranger, Pierre
AU  - Ranger P
FAU - Fahmi, Hassan
AU  - Fahmi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (15-deoxyprostaglandin J2)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-17)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
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)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Aged
MH  - Cartilage, Articular/pathology/*physiology
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/*enzymology/pathology
MH  - Dinoprostone/metabolism/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects/*physiology
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-17/pharmacology
MH  - Intramolecular Oxidoreductases/*genetics/metabolism
MH  - Microsomes/*enzymology
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*metabolism/pathology/physiopathology
MH  - PPAR gamma/metabolism
MH  - Prostaglandin D2/*analogs & derivatives/pharmacology
MH  - Prostaglandin-E Synthases
MH  - RNA, Messenger/analysis
MH  - Transcription, Genetic/drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2005/05/04 09:00
MHDA- 2005/08/10 09:00
CRDT- 2005/05/04 09:00
PHST- 2005/05/04 09:00 [pubmed]
PHST- 2005/08/10 09:00 [medline]
PHST- 2005/05/04 09:00 [entrez]
AID - 0315162X-32-887 [pii]
PST - ppublish
SO  - J Rheumatol. 2005 May;32(5):887-95.