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http://purl.uniprot.org/citations/18270204http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18270204http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18270204http://www.w3.org/2000/01/rdf-schema#comment"Macrophage activation participates pivotally in the pathophysiology of chronic inflammatory diseases, including atherosclerosis. Through the receptor EP4, prostaglandin E(2) (PGE(2)) exerts an anti-inflammatory action in macrophages, suppressing stimulus-induced expression of certain proinflammatory genes, including chemokines. We recently identified a novel EP4 receptor-associated protein (EPRAP), whose function in PGE(2)-mediated anti-inflammation remains undefined. Here we demonstrate that PGE(2) pretreatment selectively inhibits lipopolysaccharide (LPS)-induced nuclear factor kappaB1 (NF-kappaB1) p105 phosphorylation and degradation in mouse bone marrow-derived macrophages through EP4-dependent mechanisms. Similarly, directed EPRAP expression in RAW264.7 cells suppresses LPS-induced p105 phosphorylation and degradation, and subsequent activation of mitogen-activated protein kinase kinase 1/2. Forced expression of EPRAP also inhibits NF-kappaB activation induced by various proinflammatory stimuli in a concentration-dependent manner. In co-transfected cells, EPRAP, which contains multiple ankyrin repeat motifs, directly interacts with NF-kappaB1 p105/p50 and forms a complex with EP4. In EP4-overexpressing cells, PGE(2) enhances the protective action of EPRAP against stimulus-induced p105 phosphorylation, whereas EPRAP silencing in RAW264.7 cells impairs the inhibitory effect of PGE(2)-EP4 signaling on LPS-induced p105 phosphorylation. Additionally, EPRAP knockdown as well as deficiency of NF-kappaB1 in macrophages attenuates the inhibitory effect of PGE(2) on LPS-induced MIP-1beta production. Thus, PGE(2)-EP4 signaling augments NF-kappaB1 p105 protein stability through EPRAP after proinflammatory stimulation, limiting macrophage activation."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m709663200"xsd:string
http://purl.uniprot.org/citations/18270204http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m709663200"xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Shimizu K."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Shimizu K."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Aikawa M."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Aikawa M."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Okamoto Y."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Okamoto Y."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Minami M."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Minami M."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Folco E."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Folco E."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Libby P."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Libby P."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Feinberg M.W."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Feinberg M.W."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Ilasaca M.L."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/author"Ilasaca M.L."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/18270204http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string