{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:34:54Z","timestamp":1780472094778,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T00:00:00Z","timestamp":1398643200000},"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; Rheumatology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Monosodium urate monohydrate (MSU) crystal\u2013induced interleukin\u20101\u03b2 (IL\u20101\u03b2) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL\u20101\u03b2\u2013inducing factor, MSU crystals alone are insufficient to induce IL\u20101\u03b2 secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid\u2010related protein 8 (MRP\u20108) and MRP\u201014 (endogenous Toll\u2010like receptor 4 [TLR\u20104] agonists) in MSU crystal\u2013induced IL\u20101\u03b2 secretion and their relevance in gout.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MRP\u20108\/MRP\u201014 was measured in paired serum and synovial fluid samples by enzyme\u2010linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal\u2013induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP\u20108 and MRP\u201014 on MSU crystal\u2013induced IL\u20101\u03b2 secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal\u2013induced peritonitis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MRP\u20108\/MRP\u201014 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP\u20108\/MRP\u201014 was released by MSU crystal\u2013activated phagocytes and increased MSU crystal\u2013induced IL\u20101\u03b2 secretion in a TLR\u20104\u2013dependent manner. Targeted deletion of MRP\u201014 in mice led to a moderately reduced response of MSU crystal\u2013induced inflammation in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MRP\u20108 and MRP\u201014, which are highly expressed in gout, are enhancers of MSU crystal\u2013induced IL\u20101\u03b2 secretion in vitro and in vivo. These endogenous TLR\u20104 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38369","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T14:21:43Z","timestamp":1390832503000},"page":"1327-1339","source":"Crossref","is-referenced-by-count":68,"title":["Myeloid\u2010Related Proteins 8 and 14 Contribute to Monosodium Urate Monohydrate Crystal\u2013Induced Inflammation in Gout"],"prefix":"10.1002","volume":"66","author":[{"given":"Dirk","family":"Holzinger","sequence":"first","affiliation":[{"name":"University Hospital Muenster and University Children's Hospital Muenster Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Nippe","sequence":"additional","affiliation":[{"name":"University Hospital Muenster and University of Muenster Muenster 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