{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:28:24Z","timestamp":1791088104987,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,1,10]],"date-time":"2003-01-10T00:00:00Z","timestamp":1042156800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR\u03b3 in self\u2010limiting episodes of acute gouty arthritis. To do this, we investigated PPAR\u03b3 expression by monosodium urate monohydrate (MSU) crystal\u2013stimulated monocytes, and we studied the effects of PPAR\u03b3 ligands on crystal\u2010induced acute inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PPAR\u03b3 expression by MSU crystal\u2013stimulated human peripheral blood mononuclear cells was determined by reverse transcription\u2013polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR\u03b3 ligands on in vitro crystal\u2010induced cytokine production and on in vivo cellular infiltration during crystal\u2010induced acute inflammation were also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MSU crystals rapidly and selectively induced PPAR\u03b3 expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR\u03b3 was functional, since a PPAR\u03b3 ligand was able to up\u2010regulate CD36 expression on monocytes. A natural ligand of PPAR\u03b3, 15\u2010deoxy\u2010\u0394<jats:sup>12,14<\/jats:sup>\u2010prostaglandin J<jats:sub>2<\/jats:sub> (15deoxy\u2010PGJ<jats:sub>2<\/jats:sub>), significantly reduced the crystal\u2010induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy\u2010PGJ<jats:sub>2<\/jats:sub> significantly prevented cellular accumulation in a mouse air\u2010pouch model of MSU crystal\u2013induced acute inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rapid induction of PPAR\u03b3 expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10709","type":"journal-article","created":{"date-parts":[[2003,1,15]],"date-time":"2003-01-15T20:59:49Z","timestamp":1042664389000},"page":"231-239","source":"Crossref","is-referenced-by-count":70,"title":["Rapid induction of peroxisome proliferator\u2013activated receptor \u03b3 expression in human monocytes by monosodium urate monohydrate crystals"],"prefix":"10.1002","volume":"48","author":[{"given":"Tohru","family":"Akahoshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Namai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousuke","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimichi","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akito","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidero","family":"Kitasato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kameya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirobumi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,1,10]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(97)89546-0"},{"key":"e_1_2_5_3_2","first-page":"2329","volume-title":"Arthritis and allied conditions","author":"Terkeltaub RA","year":"2001"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602153340707"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1962.03050190031006"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/34.8.724"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200008)43:8<1779::AID-ANR14>3.0.CO;2-2"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013000"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1690461"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/34178"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.5.733"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.8071"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.10.1224"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199805)41:5<900::AID-ART18>3.0.CO;2-K"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81575-5"},{"key":"e_1_2_5_16_2","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.4049\/jimmunol.138.10.3213","article-title":"Interleukin 1 (IL 1) as a mediator of crystal arthritis. 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