{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:26:00Z","timestamp":1772893560917,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Modulation of the NURR subfamily of nuclear receptors may be an important mechanism regulating pathways associated with inflammatory joint disease. We examined the signaling mechanisms through which inflammatory mediators, produced by rheumatoid arthritis (RA) synovial tissue, contribute to the regulation of the NURR subfamily. Markedly enhanced expression of NURR1 is observed in synovial tissue of patients with RA compared with normal subjects. Modulation by proinflammatory mediators in primary RA and normal synoviocytes shows that PGE2, IL-1\u03b2, and TNF-\u03b1 markedly enhance NURR1 mRNA and protein levels in contrast to other subfamily members, NUR77 and NOR-1. We have established that transcriptional activation of the NURR1 gene by IL-1\u03b2 and TNF-\u03b1 requires a proximal promoter region that contains a consensus NF-\u03baB DNA-binding motif. IL-1\u03b2- and TNF-\u03b1-induced NF-\u03baB binding to this site is due predominantly to p65-p50 heterodimer and p50 homodimer subunit protein complexes. We further demonstrate a direct CREB-1-dependent regulation by PGE2 situated at promoter region \u2212171\/\u2212163. Moreover, analyses confirm the presence of CREB-1 and NF-\u03baB p50 and p65 subunit binding to the NURR1 promoter under basal conditions in freshly explanted RA synovial tissue. In summary, enhanced NF-\u03baB- and CREB-1-binding activity on the NURR1 promoter by inflammatory mediators delineates novel mechanisms in the regulation of NURR1 transcription. PGE2-, TNF-\u03b1-, and IL-1\u03b2-dependent stimulation of the NURR1 gene implies that NURR1 induction represents a point of convergence of at least two distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals.<\/jats:p>","DOI":"10.4049\/jimmunol.168.6.2979","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:31:13Z","timestamp":1398025873000},"page":"2979-2987","source":"Crossref","is-referenced-by-count":93,"title":["Activation of Nuclear Orphan Receptor NURR1 Transcription by NF-\u03baB and Cyclic Adenosine 5\u2032-Monophosphate Response Element-Binding Protein in Rheumatoid Arthritis Synovial Tissue"],"prefix":"10.1093","volume":"168","author":[{"given":"Alice N","family":"McEvoy","sequence":"first","affiliation":[{"name":"Department of Rheumatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eithne A","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiia","family":"Ponnio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orla M","family":"Conneely","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Bresnihan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn P","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St. Vincent\u2019s University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,3,15]]},"reference":[{"key":"2026020209092581400_R1","first-page":"1277","volume-title":"N. 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Med.","year":"2001"},{"key":"2026020209092581400_R11","first-page":"889","volume-title":"Science","year":"1988"},{"key":"2026020209092581400_R12","first-page":"835","volume-title":"Cell","year":"1995"},{"key":"2026020209092581400_R13","first-page":"335","volume-title":"Cell","year":"1989"},{"key":"2026020209092581400_R14","first-page":"1359","volume-title":"Mol. Endocrinol.","year":"1992"},{"key":"2026020209092581400_R15","first-page":"2129","volume-title":"Mol. Endocrinol.","year":"1992"},{"key":"2026020209092581400_R16","first-page":"8444","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1988"},{"key":"2026020209092581400_R17","first-page":"1583","volume-title":"Mol. Endocrinol.","year":"1994"},{"key":"2026020209092581400_R18","first-page":"1296","volume-title":"Science","year":"1991"},{"key":"2026020209092581400_R19","first-page":"1959","volume-title":"Biochem. Biophys. Res. Commun.","year":"1994"},{"key":"2026020209092581400_R20","first-page":"169","volume-title":"Gene Expression","year":"1996"},{"key":"2026020209092581400_R21","first-page":"39","volume-title":"Mol. Endocrinol.","year":"1997"},{"key":"2026020209092581400_R22","first-page":"2392","volume-title":"Endocrinology","year":"2000"},{"key":"2026020209092581400_R23","first-page":"183","volume-title":"Neuron","year":"1988"},{"key":"2026020209092581400_R24","first-page":"8855","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2026020209092581400_R25","first-page":"6124","volume-title":"Mol. Cell. Biol.","year":"1993"},{"key":"2026020209092581400_R26","first-page":"3469","volume-title":"Mol. Cell. Biol.","year":"1994"},{"key":"2026020209092581400_R27","first-page":"663","volume-title":"Endocrinology","year":"2000"},{"key":"2026020209092581400_R28","first-page":"2219","volume-title":"Hum. Mol. 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