PMID- 15361371
OWN - NLM
STAT- MEDLINE
DCOM- 20041025
LR  - 20181113
IS  - 0003-4967 (Print)
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 63
IP  - 10
DP  - 2004 Oct
TI  - EP2/EP4 signalling inhibits monocyte chemoattractant protein-1 production induced 
      by interleukin 1beta in synovial fibroblasts.
PG  - 1197-204
AB  - BACKGROUND: Besides its proinflammatory properties, prostaglandin E(2) (PGE(2)) 
      acts as a regulator of the expression of inducible genes. Inhibition of PGE(2) 
      synthesis might thus result in a paradoxical deleterious effect on inflammation. 
      OBJECTIVE: To examine the effect of PGE(2) on monocyte chemoattractant protein-1 
      (MCP-1) expression in cultured synovial fibroblasts (SF) stimulated with 
      interleukin (IL)1beta. METHODS: MCP-1 expression was assessed in SF stimulated 
      with IL1beta in the presence of PGE(2) or different NSAIDs by RT-PCR or northern 
      blot and immunocytochemistry. Expression of cyclo-oxygenase (COX) isoforms was 
      studied by western blot techniques. The role of PGE(2) receptors (EP) in PGE(2) 
      action was assessed employing EP receptor subtype-specific agonists. RESULTS: 
      PGE(2) significantly inhibited IL1beta induced MCP-1 expression in SF in a dose 
      dependent manner. IL1beta increased COX-2 and did not alter COX-1 synthesis in 
      SF. 11-Deoxy-PGE(1), an EP(2)/EP(4) agonist, reproduced PGE(2) action on MCP-1 
      expression. Butaprost, a selective EP(2) agonist, was less potent than PGE(2). 
      Sulprostone, an EP(1)/EP(3) agonist, had no effect on IL1beta induced MCP-1 
      expression. Inhibition of endogenous PGE(2) synthesis by NSAIDs further enhanced 
      MCP-1 mRNA expression in IL1beta stimulated SF, an effect prevented by addition 
      of exogenous PGE(2). CONCLUSION: Activation of EP(2)/EP(4) receptors down 
      regulates the expression of MCP-1 in IL1beta stimulated SF, while PGE(2) 
      pharmacological inhibition cuts off this signalling pathway and results in a 
      superinduction of MCP-1 expression. The data suggest that NSAIDs may intercept a 
      natural regulatory circuit controlling the magnitude of inflammation, which 
      questions their continuous administration in inflammatory joint diseases.
FAU - Largo, R
AU  - Largo R
AD  - Rheumatology Department, Fundacion Jimenez Diaz, Avenida Reyes Catolicos 2, 28040 
      Madrid, Spain.
FAU - Diez-Ortego, I
AU  - Diez-Ortego I
FAU - Sanchez-Pernaute, O
AU  - Sanchez-Pernaute O
FAU - Lopez-Armada, M J
AU  - Lopez-Armada MJ
FAU - Alvarez-Soria, M A
AU  - Alvarez-Soria MA
FAU - Egido, J
AU  - Egido J
FAU - Herrero-Beaumont, G
AU  - Herrero-Beaumont G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (PTGER2 protein, human)
RN  - 0 (PTGER4 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - 0 (Recombinant Proteins)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Dinoprostone/biosynthesis/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fibroblasts/drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - NF-kappa B/physiology
MH  - RNA, Messenger/genetics
MH  - Rabbits
MH  - Receptors, Prostaglandin E/agonists/*physiology
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Receptors, Prostaglandin E, EP4 Subtype
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction
MH  - Synovial Membrane/cytology/drug effects/*metabolism
PMC - PMC1754778
EDAT- 2004/09/14 05:00
MHDA- 2004/10/27 09:00
PMCR- 2007/10/01
CRDT- 2004/09/14 05:00
PHST- 2004/09/14 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/09/14 05:00 [entrez]
PHST- 2007/10/01 00:00 [pmc-release]
AID - 63/10/1197 [pii]
AID - 10.1136/ard.2003.011163 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2004 Oct;63(10):1197-204. doi: 10.1136/ard.2003.011163.