{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:47:08Z","timestamp":1789987628905,"version":"4.0.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T00:00:00Z","timestamp":1396828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T00:00:00Z","timestamp":1396828800000},"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><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured<jats:italic>in vitro<\/jats:italic>with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and\/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-\u03b1) and interleukin (IL)-1\u03b2 in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti\u2013SHIP-1 antibody. A C57BL\/6\u00a0J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-\u03b1 and IL-1\u03b2. Consistent with<jats:italic>in vitro<\/jats:italic>observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.<\/jats:p><\/jats:sec>","DOI":"10.1186\/ar4531","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T19:59:28Z","timestamp":1396900768000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis"],"prefix":"10.1186","volume":"16","author":[{"given":"Hye Mi","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Jong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Ho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Ju","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Nan","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Il","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Jung","family":"Kee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang Bae","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Yong","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Jin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Seok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Wook","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,4,7]]},"reference":[{"key":"4175_CR1","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1172\/JCI29404","volume":"116","author":"F Martinon","year":"2006","unstructured":"Martinon F, Glimcher LH: Gout: new insights into an old disease. J Clin Invest. 2006, 116: 2073-2075. 10.1172\/JCI29404.","journal-title":"J Clin Invest"},{"key":"4175_CR2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature04516","volume":"440","author":"F Martinon","year":"2006","unstructured":"Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J: Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006, 440: 237-241. 10.1038\/nature04516.","journal-title":"Nature"},{"key":"4175_CR3","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016\/S0092-8674(04)00045-5.","journal-title":"Cell"},{"key":"4175_CR4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nri2708","volume":"10","author":"RM O\u2019Connell","year":"2010","unstructured":"O\u2019Connell RM, Rao DS, Chaudhuri AA, Baltimore D: Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010, 10: 111-122. 10.1038\/nri2708.","journal-title":"Nat Rev Immunol"},{"key":"4175_CR5","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.tcb.2006.12.007","volume":"17","author":"RS Pillai","year":"2007","unstructured":"Pillai RS, Bhattacharyya SN, Filipowicz W: Repression of protein synthesis by miRNAs: how many mechanisms?. Trends Cell Biol. 2007, 17: 118-126. 10.1016\/j.tcb.2006.12.007.","journal-title":"Trends Cell Biol"},{"key":"4175_CR6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/ni1575","volume":"9","author":"C Xiao","year":"2008","unstructured":"Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008, 9: 405-414. 10.1038\/ni1575.","journal-title":"Nat Immunol"},{"key":"4175_CR7","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1126\/science.1141229","volume":"316","author":"TH Thai","year":"2007","unstructured":"Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K: Regulation of the germinal center response by microRNA-155. Science. 2007, 316: 604-608. 10.1126\/science.1141229.","journal-title":"Science"},{"key":"4175_CR8","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1126\/science.1139253","volume":"316","author":"A Rodriguez","year":"2007","unstructured":"Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A: Requirement of bic\/microRNA-155 for normal immune function. Science. 2007, 316: 608-611. 10.1126\/science.1139253.","journal-title":"Science"},{"key":"4175_CR9","doi-asserted-by":"publisher","first-page":"11193","DOI":"10.1073\/pnas.1019536108","volume":"108","author":"M Kurowska-Stolarska","year":"2011","unstructured":"Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB: MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011, 108: 11193-11198. 10.1073\/pnas.1019536108.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4175_CR10","doi-asserted-by":"publisher","first-page":"R101","DOI":"10.1186\/ar2493","volume":"10","author":"KM Pauley","year":"2008","unstructured":"Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK: Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008, 10: R101-10.1186\/ar2493.","journal-title":"Arthritis Res Ther"},{"key":"4175_CR11","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1002\/art.23386","volume":"58","author":"J Stanczyk","year":"2008","unstructured":"Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D: Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008, 58: 1001-1009. 10.1002\/art.23386.","journal-title":"Arthritis Rheum"},{"key":"4175_CR12","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1002\/art.30281","volume":"63","author":"S Bluml","year":"2011","unstructured":"Bluml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, Koenders MI, van den Berg WB, Smolen J, Redlich K: Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum. 2011, 63: 1281-1288. 10.1002\/art.30281.","journal-title":"Arthritis Rheum"},{"key":"4175_CR13","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/art.21633","volume":"54","author":"Y Murakami","year":"2006","unstructured":"Murakami Y, Akahoshi T, Hayashi I, Endo H, Kawai S, Inoue M, Kondo H, Kitasato H: Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals. Arthritis Rheum. 2006, 54: 455-462. 10.1002\/art.21633.","journal-title":"Arthritis Rheum"},{"key":"4175_CR14","doi-asserted-by":"publisher","first-page":"e7475","DOI":"10.1371\/journal.pone.0007475","volume":"4","author":"D Pilling","year":"2009","unstructured":"Pilling D, Fan T, Huang D, Kaul B, Gomer RH: Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One. 2009, 4: e7475-10.1371\/journal.pone.0007475.","journal-title":"PLoS One"},{"key":"4175_CR15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","volume":"10","author":"F Martinon","year":"2002","unstructured":"Martinon F, Burns K, Tschopp J: The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002, 10: 417-426. 10.1016\/S1097-2765(02)00599-3.","journal-title":"Mol Cell"},{"key":"4175_CR16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0022-3565(24)37005-3","volume":"283","author":"SJ Getting","year":"1997","unstructured":"Getting SJ, Flower RJ, Parente L, de Medicis R, Lussier A, Woliztky BA, Martins MA, Perretti M: Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins. J Pharmacol Exp Ther. 1997, 283: 123-130.","journal-title":"J Pharmacol Exp Ther"},{"key":"4175_CR17","doi-asserted-by":"publisher","first-page":"7113","DOI":"10.1073\/pnas.0902636106","volume":"106","author":"RM O\u2019Connell","year":"2009","unstructured":"O\u2019Connell RM, Chaudhuri AA, Rao DS, Baltimore D: Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A. 2009, 106: 7113-7118. 10.1073\/pnas.0902636106.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4175_CR18","doi-asserted-by":"publisher","first-page":"e8508","DOI":"10.1371\/journal.pone.0008508","volume":"4","author":"TJ Cremer","year":"2009","unstructured":"Cremer TJ, Ravneberg DH, Clay CD, Piper-Hunter MG, Marsh CB, Elton TS, Gunn JS, Amer A, Kanneganti TD, Schlesinger LS, Butchar JP, Tridandapani S: MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response. PLoS One. 2009, 4: e8508-10.1371\/journal.pone.0008508.","journal-title":"PLoS One"},{"key":"4175_CR19","doi-asserted-by":"publisher","first-page":"4085","DOI":"10.1038\/onc.2011.579","volume":"31","author":"DW Lee","year":"2012","unstructured":"Lee DW, Futami M, Carroll M, Feng Y, Wang Z, Fernandez M, Whichard Z, Chen Y, Kornblau S, Shpall EJ, Bueso-Ramos CE, Corey SJ: Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155. Oncogene. 2012, 31: 4085-4094. 10.1038\/onc.2011.579.","journal-title":"Oncogene"},{"key":"4175_CR20","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1172\/JCI115142","volume":"87","author":"FS di Giovine","year":"1991","unstructured":"di Giovine FS, Malawista SE, Thornton E, Duff GW: Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest. 1991, 87: 1375-1381. 10.1172\/JCI115142.","journal-title":"J Clin Invest"},{"key":"4175_CR21","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1073\/pnas.0610731104","volume":"104","author":"RM O\u2019Connell","year":"2007","unstructured":"O\u2019Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007, 104: 1604-1609. 10.1073\/pnas.0610731104.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4175_CR22","doi-asserted-by":"publisher","first-page":"5082","DOI":"10.4049\/jimmunol.179.8.5082","volume":"179","author":"E Tili","year":"2007","unstructured":"Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM: Modulation of miR-155 and miR-125b levels following lipopolysaccharide\/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007, 179: 5082-5089. 10.4049\/jimmunol.179.8.5082.","journal-title":"J Immunol"},{"key":"4175_CR23","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1002\/art.21238","volume":"52","author":"R Liu-Bryan","year":"2005","unstructured":"Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R: Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005, 52: 2936-2946. 10.1002\/art.21238.","journal-title":"Arthritis Rheum"},{"key":"4175_CR24","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s12026-008-8078-1","volume":"43","author":"WH Leung","year":"2009","unstructured":"Leung WH, Tarasenko T, Bolland S: Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes. Immunol Res. 2009, 43: 243-251. 10.1007\/s12026-008-8078-1.","journal-title":"Immunol Res"},{"key":"4175_CR25","doi-asserted-by":"publisher","first-page":"4685","DOI":"10.1182\/blood-2005-01-0191","volume":"105","author":"H An","year":"2005","unstructured":"An H, Xu H, Zhang M, Zhou J, Feng T, Qian C, Qi R, Cao X: Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3\u00a0K-independent mechanism. Blood. 2005, 105: 4685-4692. 10.1182\/blood-2005-01-0191.","journal-title":"Blood"},{"key":"4175_CR26","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.bcp.2011.05.031","volume":"82","author":"C Conde","year":"2011","unstructured":"Conde C, Gloire G, Piette J: Enzymatic and non-enzymatic activities of SHIP-1 in signal transduction and cancer. Biochem Pharmacol. 2011, 82: 1320-1334. 10.1016\/j.bcp.2011.05.031.","journal-title":"Biochem Pharmacol"},{"key":"4175_CR27","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1111\/j.1365-2249.2004.02563.x","volume":"137","author":"T McNearney","year":"2004","unstructured":"McNearney T, Baethge BA, Cao S, Alam R, Lisse JR, Westlund KN: Excitatory amino acids, TNF-alpha, and chemokine levels in synovial fluids of patients with active arthropathies. Clin Exp Immunol. 2004, 137: 621-627. 10.1111\/j.1365-2249.2004.02563.x.","journal-title":"Clin Exp Immunol"},{"key":"4175_CR28","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1136\/ard.2010.145821","volume":"70","author":"YH Chen","year":"2011","unstructured":"Chen YH, Hsieh SC, Chen WY, Li KJ, Wu CH, Wu PC, Tsai CY, Yu CL: Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFbeta1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3. Ann Rheum Dis. 2011, 70: 1655-1663. 10.1136\/ard.2010.145821.","journal-title":"Ann Rheum Dis"},{"key":"4175_CR29","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1053\/j.gastro.2011.07.038","volume":"141","author":"K Bakirtzi","year":"2011","unstructured":"Bakirtzi K, Hatziapostolou M, Karagiannides I, Polytarchou C, Jaeger S, Iliopoulos D, Pothoulakis C: Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. Gastroenterology. 2011, 141: 1749-1761. 10.1053\/j.gastro.2011.07.038.","journal-title":"Gastroenterology"},{"key":"4175_CR30","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1158\/0008-5472.CAN-09-4250","volume":"70","author":"S Jiang","year":"2010","unstructured":"Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED: MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Can Res. 2010, 70: 3119-3127. 10.1158\/0008-5472.CAN-09-4250.","journal-title":"Can Res"},{"key":"4175_CR31","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.immuni.2010.09.009","volume":"33","author":"RM O\u2019Connell","year":"2010","unstructured":"O\u2019Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D: MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010, 33: 607-619. 10.1016\/j.immuni.2010.09.009.","journal-title":"Immunity"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar4531.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar4531\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar4531.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T09:01:05Z","timestamp":1746176465000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar4531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,7]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,4]]}},"alternative-id":["4175"],"URL":"https:\/\/doi.org\/10.1186\/ar4531","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,7]]},"assertion":[{"value":"5 July 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R88"}}