Evidence map›Paper›PMID 15361371›Full record

ArticleAnnals of the rheumatic diseases2004

EP2/EP4 signalling inhibits monocyte chemoattractant protein-1 production induced by interleukin 1beta in synovial fibroblasts.

R Largo, I Díez-Ortego, O Sanchez-Pernaute, M J López-Armada, M A Alvarez-Soria, J Egido, G Herrero-Beaumont

Open access · bronzeAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 42 citations in OpenAlex.

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  7. Prostaglandin EProstaglandins & other lipid mediators · 2019
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  11. Genetic polymorphism of CCL2-2518, CXCL10-201, IL8+781 and susceptibility to severity of Enterovirus-71 infection in a Chinese population.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2014
    Article
  12. Article
  13. The cardinal role of the phospholipase A(2)/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E(2) (PCPP) axis in inflammostasis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2011
    Review
  14. Emerging roles of PGE2 receptors in models of neurological disease.Prostaglandins & other lipid mediators · 2010
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

R LargoRheumatology Department, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
I Díez-Ortego
O Sanchez-Pernaute
M J López-Armada
M A Alvarez-Soria
J Egido
G Herrero-Beaumont
Hospital Universitario Fundación Jiménez Díaz · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBesides 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.

objectiveTo examine the effect of PGE(2) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured synovial fibroblasts (SF) stimulated with interleukin (IL)1beta.

methodsMCP-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.

resultsPGE(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).

conclusionActivation 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.

Indexed as

AnimalsAnti-Inflammatory Agents, Non-SteroidalCells, CulturedChemokine CCL2DinoprostoneDose-Response Relationship, DrugFibroblastsGene Expression RegulationHumansInterleukin-1NF-kappa BRabbitsReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeRecombinant ProteinsAnti-Inflammatory Agents, Non-SteroidalChemokine CCL2DinoprostoneInterleukin-1NF-kappa BPTGER2 protein, humanPTGER4 protein, humanReceptors, Prostaglandin EReceptors, Prostaglandin E, EP2 SubtypeReceptors, Prostaglandin E, EP4 SubtypeRecombinant ProteinsRNA, Messenger

Identifiers

PMID15361371
PMCPMC1754778
OpenAlexW1993119411

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.