{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:24:28Z","timestamp":1787019868029,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T00:00:00Z","timestamp":1341360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T00:00:00Z","timestamp":1341360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated\n                      <jats:italic>in vitro<\/jats:italic>\n                      using human cell lines or monocytes of healthy volunteers. In the present study, we have investigated the effect of MSU crystals and of their combination with TLR ligands in peripheral blood mononuclear cells (PBMC) of patients with gout.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PBMCs from 18 patients with primary gout and 12 healthy donors were exposed to MSU crystals in the presence or absence of saturated fatty acid C18:0 (free fatty acid, TLR2 ligand), palmitoyl-3-cystein (Pam\n                      <jats:sub>3<\/jats:sub>\n                      Cys, TLR1\/2 ligand) and fibroblast stimulating factor-1 (FSL-1, TLR 2\/6 ligand). Production of IL-1\u03b2, IL-6, IL-8, IL-17 and tumor necrosis factor alpha (TNF\u03b1) was determined by ELISA. mRNA transcripts of IL-1\u03b2 were measured by real-time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MSU crystals alone failed to induce IL-1\u03b2, IL-6 or TNF\u03b1 in both patients and control groups, but a stronger synergy between MSU\/Pam\n                      <jats:sub>3<\/jats:sub>\n                      Cys and MSU\/C18:0 for the induction of IL-1\u03b2 was found in patients with gout compared to healthy controls. IL-6, but not IL-8, followed the kinetics of IL-1\u03b2. No production of the neutrophil-recruiting IL-17 was detectable after stimulation of the patients' PBMCs with MSU in both the presence or absence of TLR ligands. No change of gene transcripts of IL-1\u03b2 after stimulation with MSU and Pam\n                      <jats:sub>3<\/jats:sub>\n                      Cys or with MSU and C18:0 was found. A positive correlation was found between synergy in IL-1\u03b2 production from PBMCs of patients between C18:0 and MSU crystals, as well as the annual number of attacks of acute gouty arthritis (r\n                      <jats:sub>s<\/jats:sub>\n                      : +0.649,\n                      <jats:italic>P<\/jats:italic>\n                      : 0.022).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The synergy between MSU crystals and TLR-2 ligands is more prominent in patients with gout than in controls. This is likely mediated by the enhanced maturation of pro-IL-1\u03b2 into IL-1\u03b2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/ar3898","type":"journal-article","created":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T22:59:12Z","timestamp":1341442752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Enhanced interleukin-1\u03b2 production of PBMCs from patients with gout after stimulation with Toll-like receptor-2 ligands and urate crystals"],"prefix":"10.1186","volume":"14","author":[{"given":"Eleni E","family":"Mylona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mouktaroudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania O","family":"Crisan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatoula","family":"Makri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Pistiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Georgitsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Savva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos WM","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos J","family":"Giamarellos-Bourboulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo AB","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,7,4]]},"reference":[{"key":"3654_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.metabol.2010.07.009","volume":"59","author":"TB Vanltallie","year":"2010","unstructured":"Vanltallie TB: Gout: epitome of painful arthritis. 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