{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T19:17:40Z","timestamp":1794338260958,"version":"4.9.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T00:00:00Z","timestamp":1327622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Deposition of monosodium urate monohydrate (MSU) crystals in the joints promotes an intense inflammatory response and joint dysfunction. This study evaluated the role of the NLRP3 inflammasome and 5\u2010lipoxygenase (5\u2010LOX)\u2013derived leukotriene B\n                      <jats:sub>4<\/jats:sub>\n                      (LTB\n                      <jats:sub>4<\/jats:sub>\n                      ) in driving tissue inflammation and hypernociception in a murine model of gout.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Gout was induced by injecting MSU crystals into the joints of mice. Wild\u2010type mice and mice deficient in NLRP3, ASC, caspase 1, interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20101 receptor type I (IL\u20101RI), IL\u201018R, myeloid differentiation factor 88 (MyD88), or 5\u2010LOX were used. Evaluations were performed to assess neutrophil influx, LTB\n                      <jats:sub>4<\/jats:sub>\n                      activity, cytokine (IL\u20101\u03b2, CXCL1) production (by enzyme\u2010linked immunosorbent assay), synovial microvasculature cell adhesion (by intravital microscopy), and hypernociception. Cleaved caspase 1 and production of reactive oxygen species (ROS) were analyzed in macrophages by Western blotting and fluorometric assay, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Injection of MSU crystals into the knee joints of mice induced neutrophil influx and neutrophil\u2010dependent hypernociception. MSU crystal\u2013induced neutrophil influx was CXCR2\u2010dependent and relied on the induction of CXCL1 in an NLRP3\/ASC\/caspase 1\/IL\u20101\u03b2\/MyD88\u2013dependent manner. LTB\n                      <jats:sub>4<\/jats:sub>\n                      was produced rapidly after injection of MSU crystals, and this was necessary for caspase 1\u2013dependent IL\u20101\u03b2 production and consequent release of CXCR2\u2010acting chemokines in vivo. In vitro, macrophages produced LTB\n                      <jats:sub>4<\/jats:sub>\n                      after MSU crystal injection, and LTB\n                      <jats:sub>4<\/jats:sub>\n                      was relevant in the MSU crystal\u2013induced maturation of IL\u20101\u03b2. Mechanistically, LTB\n                      <jats:sub>4<\/jats:sub>\n                      drove MSU crystal\u2013induced production of ROS and ROS\u2010dependent activation of the NLRP3 inflammasome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These results reveal the role of the NLRP3 inflammasome in mediating MSU crystal\u2013induced inflammation and dysfunction of the joints, and highlight a previously unrecognized role of LTB\n                      <jats:sub>4<\/jats:sub>\n                      in driving NLRP3 inflammasome activation in response to MSU crystals, both in vitro and in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.33355","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T22:34:39Z","timestamp":1317162879000},"page":"474-484","source":"Crossref","is-referenced-by-count":239,"title":["NLRP3 inflammasome\u2013mediated neutrophil recruitment and hypernociception depend on leukotriene B\n                    <sub>4<\/sub>\n                    in a murine model of gout"],"prefix":"10.1002","volume":"64","author":[{"given":"Fl\u00e1vio A.","family":"Amaral","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian V.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia 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