{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:46:02Z","timestamp":1791276362270,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T00:00:00Z","timestamp":1125619200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatism"],"published-print":{"date-parts":[[2005,9]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n In gout, incompletely defined molecular factors alter recognition of dormant articular and bursal monosodium urate monohydrate (MSU) crystal deposits, thereby inducing self\u2010limiting bouts of characteristically severe neutrophilic inflammation. To define primary determinants of cellular recognition, uptake, and inflammatory responses to MSU crystals, we conducted a study to test the role of Toll\u2010like receptor 2 (TLR\u20102), TLR\u20104, and the cytosolic TLR adapter protein myeloid differentiation factor 88 (MyD88), which are centrally involved in innate immune recognition of microbial pathogens.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We isolated bone marrow\u2013derived macrophages (BMDMs) in TLR\u20102\n \u2212\/\u2212<\/jats:sup>\n , TLR\u20104\n \u2212\/\u2212<\/jats:sup>\n , MyD88\n \u2212\/\u2212<\/jats:sup>\n , and congenic wild\u2010type mice, and assessed phagocytosis and cytokine expression in response to endotoxin\u2010free MSU crystals under serum\u2010free conditions. MSU crystals also were injected into mouse synovium\u2010like subcutaneous air pouches.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n TLR\u20102\n \u2212\/\u2212<\/jats:sup>\n , TLR\u20104\n \u2212\/\u2212<\/jats:sup>\n , and MyD88\n \u2212\/\u2212<\/jats:sup>\n BMDMs demonstrated impaired uptake of MSU crystals in vitro. MSU crystal\u2013induced production of interleukin\u20101\u03b2 (IL\u20101\u03b2), tumor necrosis factor \u03b1, keratinocyte\u2010derived cytokine\/growth\u2010related oncogene \u03b1, and transforming growth factor \u03b21 also were significantly suppressed in TLR\u20102\n \u2212\/\u2212<\/jats:sup>\n and TLR\u20104\n \u2212\/\u2212<\/jats:sup>\n BMDMs and were blunted in MyD88\n \u2212\/\u2212<\/jats:sup>\n BMDMs in vitro. Neutrophil influx and local induction of IL\u20101\u03b2 in subcutaneous air pouches were suppressed 6 hours after injection of MSU crystals in TLR\u20102\n \u2212\/\u2212<\/jats:sup>\n and TLR\u20104\n \u2212\/\u2212<\/jats:sup>\n mice and were attenuated in MyD88\n \u2212\/\u2212<\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The murine host requires TLR\u20102, TLR\u20104, and MyD88 for macrophage activation and development of full\u2010blown neutrophilic, air pouch inflammation in response to MSU crystals. Our findings implicate innate immune cellular recognition of naked MSU crystals by specific TLRs as a major factor in determining the inflammatory potential of MSU crystal deposits and the course of gouty arthritis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.21238","type":"journal-article","created":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T10:49:22Z","timestamp":1125658162000},"page":"2936-2946","source":"Crossref","is-referenced-by-count":347,"title":["Innate immunity conferred by toll\u2010like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal\u2013induced 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