PMID- 15314505
OWN - NLM
STAT- MEDLINE
DCOM- 20041130
LR  - 20190917
IS  - 1040-8711 (Print)
IS  - 1040-8711 (Linking)
VI  - 16
IP  - 5
DP  - 2004 Sep
TI  - mPGES-1 as a novel target for arthritis.
PG  - 623-7
AB  - PURPOSE OF REVIEW: Prostaglandin E2 (PGE2) is by far the major prostanoid 
      synthesized in the joint and plays an important role in inflammation and 
      pathogenesis of arthritis. Moreover, increased levels of PGE2 have been detected 
      in serum and synovial fluids from arthritic patients. Little was known about the 
      enzyme(s) involved in the isomerization of PGH2 into PGE2 synthesis until recent 
      identification of PGE synthase (PGES). Several isoforms were characterized, among 
      which microsomal PGES-1 (mPGES-1) has received much attention, because this 
      enzyme is inducible and functionally linked with cyclooxygenase-2. This review 
      focuses on recent findings regarding the regulation of mPGES-1 expression and the 
      possible role of this enzyme in arthritis. RECENT FINDINGS: Various in vitro and 
      in vivo studies demonstrated that proinflammatory stimuli, such as 
      interleukin-1beta and tumor necrosis factor-alpha upregulate the expression of 
      mPGES-1 at the protein and mRNA level. Promoter analysis indicates that the 
      transcription factor Egr-1 is involved in the positive regulation of mPGES-1. 
      Studies from mPGES-1-deficient mice and animal models of inflammatory arthritis 
      strongly suggest a role of mPGES-1 in the production of PGE2 and the pathogenesis 
      of arthritis. SUMMARY: This article reviews the regulation of mPGES-1 expression 
      and provides evidence for a role of mPGES-1 in inducible PGE2 production and 
      arthritis. Future studies using selective inhibitors of mPGES-1 activity or 
      expression would clarify the role of this enzyme in arthritis.
CI  - Copyright 2004 Lippincott Williams & Wilkins
FAU - Fahmi, Hassan
AU  - Fahmi H
AD  - Osteoarthritis Research Unit, Centre Hospitalier de l'Universite de Montreal, 
      Hopital Notre-Dame, Montreal, Quebec, Canada. h.fahmi@umontreal.ca
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Opin Rheumatol
JT  - Current opinion in rheumatology
JID - 9000851
RN  - 0 (Isoenzymes)
RN  - 0 (Prostaglandins E)
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  - EC 5.3.99.3 (Ptges protein, mouse)
SB  - IM
MH  - Animals
MH  - Arthritis/*enzymology/etiology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Intramolecular Oxidoreductases/*antagonists & inhibitors/genetics/*metabolism
MH  - Isoenzymes
MH  - Mice
MH  - Prostaglandin-E Synthases
MH  - Prostaglandins E/biosynthesis
MH  - Up-Regulation
RF  - 52
EDAT- 2004/08/18 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/08/18 05:00
PHST- 2004/08/18 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/08/18 05:00 [entrez]
AID - 00002281-200409000-00023 [pii]
AID - 10.1097/01.bor.0000129664.81052.8e [doi]
PST - ppublish
SO  - Curr Opin Rheumatol. 2004 Sep;16(5):623-7. doi: 
      10.1097/01.bor.0000129664.81052.8e.