{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:48:17Z","timestamp":1793908097652,"version":"4.8.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Gout is caused by monosodium urate (MSU) crystal deposition within joints. This leads to acute episodes of inflammation (\u201cgout flares\u201d) driven by NLRP3 inflammasome activation in macrophages. Gout flares are frequently present during late night\/early morning. The reason for this timing is unclear. Recent evidence suggests the NLRP3 inflammasome is under circadian control. The purpose of this study was to determine whether MSU crystals cause changes in the circadian clock in macrophages leading to time\u2010of\u2010day differences in NLRP3 inflammasome activation. Levels of circadian clock components were measured in undifferentiated \u201cmonocytic\u201d and PMA\u2010differentiated \u201cmacrophagic\u201d THP\u20101 cells cultured with\/without MSU crystals. Caspase\u20101 activity was measured to assess NLRP3 inflammasome activity. MSU crystal exposure resulted in minimal effects on clock genes in THP\u20101 monocytes but\n                    <jats:italic>BMAL1, CRY1, PER2<\/jats:italic>\n                    , and\n                    <jats:italic>REV\u2010ERB\u03b1<\/jats:italic>\n                    showed altered expression with reduced protein levels of BMAL1 and REV\u2010ERB\u03b1 in THP\u20101 macrophages. REV\u2010ERB\u03b1 activation or BMAL1 over\u2010expression resulted in reduced MSU crystal\u2010induced caspase\u20101 activity. BMAL1 knockdown resulted in a further increase in MSU crystal\u2010induced caspase\u20101 activity, but only at times of day when BMAL1 levels were naturally high. MSU crystal\u2010induced NLRP3 inflammasome activation was greatest at the time of day when BMAL1 levels were naturally low. MSU crystals alter the expression of circadian clock components in THP\u20101 macrophages leading to loss of BMAL1 and REV\u2010ERB\u03b1\u2010mediated repression of NLRP3 inflammasome activity and time\u2010of\u2010day differences in susceptibility to inflammasome activation. Our findings suggest that the nocturnal risk of gout flare is at least partially a consequence of altered circadian control of immune cell function.\n                  <\/jats:p>","DOI":"10.1096\/fj.202202035r","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T12:30:38Z","timestamp":1682598638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Monosodium urate crystals alter the circadian clock in macrophages leading to loss of\n                    <scp>NLRP3<\/scp>\n                    inflammasome repression: Implications for timing of the gout flare"],"prefix":"10.1096","volume":"37","author":[{"given":"Dmitry","family":"Popov","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology University of Auckland  Auckland New 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