{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:17:29Z","timestamp":1791001049201,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1A2B2006281"],"award-info":[{"award-number":["NRF\u20102017R1A2B2006281"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102019R1A2C2085739"],"award-info":[{"award-number":["NRF\u20102019R1A2C2085739"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1A4A1015036"],"award-info":[{"award-number":["NRF\u20102017R1A4A1015036"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102020R1A4A2002894"],"award-info":[{"award-number":["NRF\u20102020R1A4A2002894"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"Objective<\/jats:title>The NLRP<\/jats:styled-content>3 inflammasome is closely linked to the pathophysiology of a wide range of inflammatory diseases. This study was undertaken to identify small molecules that directly bind to NLRP<\/jats:styled-content>3 in order to develop pharmacologic interventions for NLRP<\/jats:styled-content>3\u2010related diseases.<\/jats:p><\/jats:sec>Methods<\/jats:title>A structure\u2010based virtual screening analysis was performed with ~62,800 compounds to select efficient NLRP<\/jats:styled-content>3 inhibitors. The production of caspase 1\u2010p10 and interleukin\u20101\u03b2 (IL<\/jats:styled-content>\u20101\u03b2) was measured by immunoblotting and enzyme\u2010linked immunosorbent assay to examine NLRP<\/jats:styled-content>3 inflammasome activation. Two gouty arthritis models and an air pouch inflammation model induced by monosodium urate monohydrate (MSU<\/jats:styled-content>) crystal injection were used for in vivo experiments. Primary synovial fluid cells from gout patients were used to determine the relevance of NLRP<\/jats:styled-content>3 inflammasome inhibition in human gout.<\/jats:p><\/jats:sec>Results<\/jats:title>Beta\u2010carotene (provitamin A) suppressed the NLRP<\/jats:styled-content>3 inflammasome activation induced by various activators, including MSU<\/jats:styled-content> crystals, in mouse bone marrow\u2013derived primary macrophages (P<\/jats:italic> < 0.05). Surface plasmon resonance analysis demonstrated the direct binding of \u03b2\u2010carotene to the pyrin domain (PYD<\/jats:styled-content>) of NLRP<\/jats:styled-content>3 (KD<\/jats:sub><\/jats:styled-content> = 3.41 \u00d7 10\u22126<\/jats:sup>). Molecular modeling and mutation assays revealed the interaction mode between \u03b2\u2010carotene and the NLRP<\/jats:styled-content>3 PYD<\/jats:styled-content>. Inflammatory symptoms induced by MSU<\/jats:styled-content> crystals were attenuated by oral administration of \u03b2\u2010carotene in gouty arthritis mouse models (P<\/jats:italic> < 0.05), correlating with its suppressive effects on the NLRP<\/jats:styled-content>3 inflammasome in inflamed tissues. Furthermore, \u03b2\u2010carotene reduced IL<\/jats:styled-content>\u20101\u03b2 secretion from human synovial fluid cells isolated from gout patients (P<\/jats:italic> < 0.05), showing its inhibitory efficacy in human gout.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our results present \u03b2\u2010carotene as a selective and direct inhibitor of NLRP<\/jats:styled-content>3, and the binding of \u03b2\u2010carotene to NLRP<\/jats:styled-content>3 PYD<\/jats:styled-content> as a novel pharmacologic strategy to combat NLRP<\/jats:styled-content>3 inflammasome\u2013driven diseases, including gouty arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41245","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T06:04:50Z","timestamp":1583388290000},"page":"1192-1202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Direct Binding to NLRP3 Pyrin Domain as a Novel Strategy to Prevent NLRP3\u2010Driven Inflammation and Gouty Arthritis"],"prefix":"10.1002","volume":"72","author":[{"given":"Gabsik","family":"Yang","sequence":"first","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye E.","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Jin","family":"Moon","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Uijeongbu, Republic of Korea, and The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung M.","family":"Ko","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Bucheon, Republic of Korea, and The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung H.","family":"Koh","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Bucheon, Republic of Korea, and The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin K.","family":"Seok","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Ki","family":"Min","sequence":"additional","affiliation":[{"name":"St. Mary's Hospital, Bucheon, Republic of Korea, and The Catholic University of Korea Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae\u2010Hwe","family":"Heo","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han C.","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Yeon","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye S.","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy The Catholic University of Korea Bucheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School 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