{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:04:11Z","timestamp":1789772651716,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T00:00:00Z","timestamp":1269561600000},"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":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The mechanism by which monosodium urate monohydrate (MSU) crystals intracellularly activate the cryopyrin inflammasome is unknown. The aim of this study was to use a mouse molecular genetics\u2013based approach to test whether the leucine\u2010rich repeat (LRR) domain of cryopyrin is required for MSU crystal\u2013induced inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cryopyrin\u2010knockout <jats:italic>lacZ<\/jats:italic> (Cryo<jats:sup>\u2212Z\/\u2212Z<\/jats:sup>) mice and mice with the cryopyrin LRR domain deleted and fused to the <jats:italic>lacZ<\/jats:italic> reporter (Cryo<jats:sup>\u0394LRR Z\/\u0394LRR Z<\/jats:sup>) were generated using bacterial artificial chromosome\u2013based targeting vectors, which allow for large genomic deletions. Bone marrow\u2013derived macrophages from Cryo<jats:sup>\u0394LRR Z\/\u0394LRR Z<\/jats:sup> mice, Cryo<jats:sup>\u2212Z\/\u2212Z<\/jats:sup> mice, and congenic wild\u2010type (WT) mice were challenged with endotoxin\u2010free MSU crystals under serum\u2010free conditions. Phagocytosis and cytokine expression were assessed by flow cytometry and enzyme\u2010linked immunosorbent assay. MSU crystals also were injected into mouse synovial\u2010like subcutaneous air pouches. The in vivo inflammatory responses were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Release of interleukin\u20101\u03b2 (IL\u20101\u03b2), but not CXCL1 and tumor necrosis factor \u03b1, was impaired in Cryo<jats:sup>\u0394LRR Z\/\u0394LRR Z<\/jats:sup> and Cryo<jats:sup>\u2212Z\/\u2212Z<\/jats:sup> mouse bone marrow\u2013derived macrophages compared with WT mouse bone marrow\u2013derived macrophages in response to not only MSU crystals but also other known stimuli that activate the cryopyrin inflammasome. In addition, a comparable percentage of MSU crystals taken up by each type of bone marrow\u2013derived macrophage was observed. Moreover, total leukocyte infiltration in the air pouch and IL\u20101\u03b2 production were attenuated in Cryo<jats:sup>\u2212Z\/\u2212Z<\/jats:sup> and Cryo<jats:sup>\u0394LRR Z\/\u0394LRR Z<\/jats:sup> mice at 6 hours postinjection of MSU crystals compared with WT mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MSU crystal\u2013induced inflammatory responses were comparably attenuated both in vitro and in vivo in Cryo<jats:sup>\u0394LRR Z\/\u0394LRR Z<\/jats:sup> and Cryo<jats:sup>\u2212Z\/\u2212Z<\/jats:sup> mice. Hence, the LRR domain of cryopyrin plays a role in mediating MSU crystal\u2013induced inflammation in this model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27456","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T19:01:31Z","timestamp":1269630091000},"page":"2170-2179","source":"Crossref","is-referenced-by-count":62,"title":["Role of the leucine\u2010rich repeat domain of cryopyrin\/NALP3 in monosodium urate crystal\u2013induced inflammation in mice"],"prefix":"10.1002","volume":"62","author":[{"given":"Hal M.","family":"Hoffman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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