{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:48:21Z","timestamp":1793908101895,"version":"4.8.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STE2437\/2-1"],"award-info":[{"award-number":["STE2437\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AN372\/14-3"],"award-info":[{"award-number":["AN372\/14-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"LMUexcellent initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although monosodium urate (MSU) crystals are known to trigger inflammation, published data on soluble uric acid (sUA) in this context are discrepant. We hypothesized that diverse sUA preparation methods account for this discrepancy and that an animal model with clinically relevant levels of asymptomatic hyperuricemia and gouty arthritis can ultimately clarify this issue. To test this, we cultured human monocytes with different sUA preparation solutions and found that solubilizing uric acid (UA) by prewarming created erroneous results because of UA microcrystal contaminants triggering IL-1\u03b2 release. Solubilizing UA with NaOH avoided this artifact, and this microcrystal-free preparation suppressed LPS- or MSU crystal\u2013induced monocyte activation, a process depending on the intracellular uptake of sUA via the urate transporter SLC2A9\/GLUT9. CD14+ monocytes isolated from hyperuricemic patients were less responsive to inflammatory stimuli compared with monocytes from healthy individuals. Treatment with plasma from hyperuricemic patients impaired the inflammatory function of CD14+ monocytes, an effect fully reversible by removing sUA from hyperuricemic plasma. Moreover, Alb-creERT2;Glut9lox\/lox mice with hyperuricemia (serum UA of 9\u201311 mg\/dl) showed a suppressed inflammatory response to MSU crystals compared with Glut9lox\/lox controls without hyperuricemia. Taken together, we unravel a technical explanation for discrepancies in the published literature on immune effects of sUA and identify hyperuricemia as an intrinsic suppressor of innate immunity, in which sUA modulates the capacity of monocytes to respond to danger signals. Thus, sUA is not only a substrate for the formation of MSU crystals but also an intrinsic inhibitor of MSU crystal\u2013induced tissue inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.2000319","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T18:55:14Z","timestamp":1592592914000},"page":"789-800","source":"Crossref","is-referenced-by-count":63,"title":["Soluble Uric Acid Is an Intrinsic Negative Regulator of Monocyte Activation in Monosodium Urate Crystal\u2013Induced Tissue Inflammation"],"prefix":"10.1093","volume":"205","author":[{"given":"Qiuyue","family":"Ma","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-7442","authenticated-orcid":false,"given":"Mohsen","family":"Honarpisheh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-584X","authenticated-orcid":false,"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Sellmayr","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Lindenmeyer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]},{"name":"III. Department of Medicine, University Medical Center Hamburg-Eppendorf , 20246 Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"B\u00f6hland","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Romagnani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Experimental and Clinical Sciences \u201cMaria Serio,\u201d University of Florence , 50139 Florence ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Anders","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-494X","authenticated-orcid":false,"given":"Stefanie","family":"Steiger","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig Maximilian University of Munich , 80336 Munich, Bavaria ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"2025030417504503400_r1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/oxfordjournals.molbev.a004123","article-title":"Loss of urate oxidase activity in hominoids and its evolutionary implications","volume":"19","author":"Oda","year":"2002","journal-title":"Mol. 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