ArticleAnnals of the rheumatic diseases2004
EP2/EP4 signalling inhibits monocyte chemoattractant protein-1 production induced by interleukin 1beta in synovial fibroblasts.
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.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac.Annals of the rheumatic diseases · 2006Trial
- MSC administration resolves experimental acute gout increasing specialized pro-resolving mediators synthesis through a super-induction of prostaglandin EStem cell research & therapy · 2025Article
- Impact of intra-articular high-concentration hyaluronic acid administration on the innate immune response in experimental knee osteoarthritis.BMC musculoskeletal disorders · 2025Article
- The effect of ITLN1, XCL2 and DOT1L variants on knee osteoarthritis risk in the Han population.Archives of orthopaedic and trauma surgery · 2023Article
- Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.Acta pharmaceutica Sinica. B · 2021Article
- Celecoxib alleviates pathological cardiac hypertrophy and fibrosis via M1-like macrophage infiltration in neonatal mice.iScience · 2021Article
- Prostaglandin EProstaglandins & other lipid mediators · 2019Article
- VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Characterization of Eicosanoids Produced by Adipocyte Lipolysis: IMPLICATION OF CYCLOOXYGENASE-2 IN ADIPOSE INFLAMMATION.The Journal of biological chemistry · 2016Article
- The Prostaglandin E2 Receptor EP4 Regulates Obesity-Related Inflammation and Insulin Sensitivity.PloS one · 2015Article
- 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.] · 2014Article
- 5-Lipoxygenase inhibitors attenuate TNF-α-induced inflammation in human synovial fibroblasts.PloS one · 2014Article
- 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.] · 2011Review
- Emerging roles of PGE2 receptors in models of neurological disease.Prostaglandins & other lipid mediators · 2010Review
- Prostaglandin E2 differentially modulates proinflammatory/prodestructive effects of TNF-alpha on synovial fibroblasts via specific E prostanoid receptors/cAMP.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis.Arthritis and rheumatism · 2009Article
- Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation.The Journal of biological chemistry · 2008Article
- Prostaglandin E2 receptors EP1 and EP4 are up-regulated in rabbit chondrocytes by IL-1beta, but not by TNFalpha.Rheumatology international · 2007Article
- Prostanoids as friends, not foes: further evidence from the interference by cycloxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats.Inflammopharmacology · 2005Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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