{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:23:40Z","timestamp":1791350620984,"version":"4.3.1"},"reference-count":52,"publisher":"The Journal of Rheumatology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Microsomal prostaglandin E<jats:sub>2<\/jats:sub>synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE<jats:sub>2<\/jats:sub>. Early growth response factor-1 (Egr-1) is a key transcription factor in the regulation of mPGES-1, and its activity is negatively regulated by the corepressor NGF1-A-binding protein-1 (NAB1). We examined the effects of valproic acid (VA), a histone deacetylase inhibitor, on interleukin 1\u00df (IL-1\u00df)-induced mPGES-1 expression in human chondrocytes, and evaluated the roles of Egr-1 and NAB1 in these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Chondrocytes were stimulated with IL-1 in the absence or presence of VA, and the level of mPGES-1 protein and mRNA expression were evaluated using Western blotting and real-time reverse-transcription polymerase chain reaction (PCR), respectively. mPGES-1 promoter activity was analyzed in transient transfection experiments. Egr-1 and NAB1 recruitment to the mPGES-1 promoter was evaluated using chromatin immunoprecipitation assays. Small interfering RNA (siRNA) approaches were used to silence NAB1 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>VA dose-dependently suppressed IL-1-induced mPGES-1 protein and mRNA expression as well as its promoter activation. Treatment with VA did not alter IL-1-induced Egr-1 expression, or its recruitment to the mPGES-1 promoter, but prevented its transcriptional activity. The suppressive effect of VA requires<jats:italic>de novo<\/jats:italic>protein synthesis. VA induced the expression of NAB1, and its recruitment to the mPGES-1 promoter, suggesting that NAB1 may mediate the suppressive effect of VA. Indeed, NAB1 silencing with siRNA blocked VA-mediated suppression of IL-1-induced mPGES-1 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>VA inhibited IL-1-induced mPGES-1 expression in chondrocytes. The suppressive effect of VA was not due to reduced expression or recruitment of Egr-1 to the mPGES-1 promoter and involved upregulation of NAB1.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.100907","type":"journal-article","created":{"date-parts":[[2011,1,16]],"date-time":"2011-01-16T01:12:54Z","timestamp":1295140374000},"page":"492-502","source":"Crossref","is-referenced-by-count":13,"title":["Valproic Acid Suppresses Interleukin-1\u00df-induced Microsomal Prostaglandin E<sub>2<\/sub>Synthase-1 Expression in Chondrocytes Through Upregulation of NAB1"],"prefix":"10.3899","volume":"38","author":[{"given":"NADIA","family":"ZAYED","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FATIMA EZZAHRA","family":"EL MANSOURI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NADIR","family":"CHABANE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MOHIT","family":"KAPOOR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOHANNE","family":"MARTEL-PELLETIER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MOHAMED","family":"BENDERDOUR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JEAN-PIERRE","family":"PELLETIER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NICOLAS","family":"DUVAL","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HASSAN","family":"FAHMI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2018112909260750000_38.3.492.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119280"},{"key":"2018112909260750000_38.3.492.2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10356"},{"key":"2018112909260750000_38.3.492.3","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.4049\/jimmunol.155.7.3570","article-title":"Superantigen-induced collagenase gene expression in human IFN-gamma-treated fibroblast-like synoviocytes involves prostaglandin E2. 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