{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:59:47Z","timestamp":1792673987304,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,7,3]],"date-time":"2017-07-03T00:00:00Z","timestamp":1499040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China Grant","doi-asserted-by":"publisher","award":["81430099"],"award-info":[{"award-number":["81430099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002829","name":"Projects of International Cooperation and Exchanges Grant","doi-asserted-by":"publisher","award":["2014DFA32950"],"award-info":[{"award-number":["2014DFA32950"]}],"id":[{"id":"10.13039\/100002829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002888","name":"Beijing Municipal Commission of Education grant","doi-asserted-by":"publisher","award":["521\/0101312"],"award-info":[{"award-number":["521\/0101312"]}],"id":[{"id":"10.13039\/501100002888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic immune inflammatory disease mediated by the influx of immune cells into the synovial joint space. As Tanshinone IIA (TIIA) has potent anti-oxidant and anti-inflammatory activities, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TIIA on RA and immune cell activation. The anti-arthritic activity of TIIA was investigated in an adjuvant-induced arthritis model of RA in mice. Myeloperoxidase and neutrophil elastase expression levels were assessed in ankle joints by immunohistochemistry analysis. Immune cell infiltration was evaluated in air pouch experiments. Proinflammatory cytokines expression levels were determined by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. Neutrophil extracellular traps (NETs) were assessed by immunostaining and confocal microscopy. Treatment with TIIA alleviated cartilage erosion and neutrophil infiltration in the ankle joints of AA mice and reduced proinflammatory cytokine expression levels in sera. TIIA suppressed interleukin-6 and tumour necrosis factor-\u03b1 expression and release in neutrophils and promoted neutrophil apoptosis. TIIA also inhibited the NET formation of neutrophils. Our findings demonstrated that TIIA can ameliorate RA effectively by targeting neutrophils, indicating that TIIA may act as a potential therapeutic for RA.<\/jats:p>","DOI":"10.1111\/cei.12993","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T16:59:14Z","timestamp":1495731554000},"page":"29-39","source":"Crossref","is-referenced-by-count":44,"title":["Tanshinone IIA ameliorates chronic arthritis in mice by modulating neutrophil activities"],"prefix":"10.1093","volume":"190","author":[{"given":"S","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Sheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-3494","authenticated-orcid":false,"given":"A","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China"},{"name":"State Key Laboratory of Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,3]]},"reference":[{"key":"2021120808183187600_cei12993-bib-0001","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.autrev.2009.12.013","article-title":"Neutrophils in rheumatoid arthritis: more than simple final effectors","volume":"9","author":"Casc\u00e3o","year":"2010","journal-title":"Autoimmun Rev"},{"key":"2021120808183187600_cei12993-bib-0002","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrrheum.2014.80","article-title":"The multifactorial role of neutrophils in rheumatoid arthritis","volume":"10","author":"Wright","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0003","doi-asserted-by":"crossref","first-page":"R120","DOI":"10.1186\/ar2009","article-title":"Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid arthritis","volume":"8","author":"Raza","year":"2006","journal-title":"Arthritis Res Ther"},{"key":"2021120808183187600_cei12993-bib-0004","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ncprheum0291","article-title":"Granulocyte colony-stimulating factor and neutrophils\u2013forgotten mediators of inflammatory disease","volume":"2","author":"Eyles","year":"2006","journal-title":"Nat Clin Pract Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0005","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1182\/blood-2004-12-4942","article-title":"ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-alpha-activated vascular endothelium under flow","volume":"106","author":"Yang","year":"2005","journal-title":"Blood"},{"key":"2021120808183187600_cei12993-bib-0006","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/MOH.0b013e3283333930","article-title":"Recent developments and complexities in neutrophil transmigration","volume":"17","author":"Woodfin","year":"2010","journal-title":"Curr Opin Hematol"},{"key":"2021120808183187600_cei12993-bib-0007","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrrheum.2015.171","article-title":"Cytokines in rheumatoid arthritis \u2013 shaping the immunological landscape","volume":"12","author":"McInnes","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0008","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nri2094","article-title":"Cytokines in the pathogenesis of rheumatoid arthritis","volume":"7","author":"McInnes","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2021120808183187600_cei12993-bib-0009","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nrrheum.2015.8","article-title":"Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges","volume":"11","author":"Smolen","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0010","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/ncprheum0727","article-title":"Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair?","volume":"4","author":"Murphy","year":"2008","journal-title":"Nat Clin Pract Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0011","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/ar4325","article-title":"Role of neutrophils in systemic autoimmune diseases","volume":"15","author":"Kaplan","year":"2013","journal-title":"Arthritis Res Ther"},{"key":"2021120808183187600_cei12993-bib-0012","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1002\/art.39283","article-title":"Local Joint inflammation and histone citrullination in a murine model of the transition from preclinical autoimmunity to inflammatory arthritis","volume":"67","author":"Sohn","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2021120808183187600_cei12993-bib-0013","doi-asserted-by":"crossref","first-page":"178ra40","DOI":"10.1126\/scitranslmed.3005580","article-title":"NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis","volume":"5","author":"Khandpur","year":"2013","journal-title":"Sci Transl Med"},{"key":"2021120808183187600_cei12993-bib-0014","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/aps.2014.112","article-title":"Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice","volume":"36","author":"Xu","year":"2015","journal-title":"Acta Pharmacol Sin"},{"key":"2021120808183187600_cei12993-bib-0015","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jsbmb.2009.01.011","article-title":"The anti-inflammatory activities of Tanshinone IIA, an active component of TCM, are mediated by estrogen receptor activation and inhibition of iNOS","volume":"113","author":"Fan","year":"2009","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2021120808183187600_cei12993-bib-0016","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/ptr.3278","article-title":"Regulation of adhesion molecules expression in TNF-\u03b1-stimulated brain microvascular endothelial cells by tanshinone IIA: involvement of NF-\u03baB and ROS generation","volume":"25","author":"Tang","year":"2011","journal-title":"Phytother Res"},{"key":"2021120808183187600_cei12993-bib-0017","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1126\/scitranslmed.3007672","article-title":"A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism","volume":"6","author":"Robertson","year":"2014","journal-title":"Sci Transl Med"},{"key":"2021120808183187600_cei12993-bib-0018","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1172\/JCI16913","article-title":"Essential role for proteinase-activated receptor-2 in arthritis","volume":"111","author":"Ferrell","year":"2003","journal-title":"J Clin Invest"},{"key":"2021120808183187600_cei12993-bib-0019","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.4049\/jimmunol.172.5.2795","article-title":"The T cells specific for the carboxyl-terminal determinants of self (rat) heat-shock protein 65 escape tolerance induction and are involved in regulation of autoimmune arthritis","volume":"172","author":"Durai","year":"2004","journal-title":"J Immunol"},{"key":"2021120808183187600_cei12993-bib-0020","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.intimp.2013.09.024","article-title":"Curcumin inhibits agent-induced human neutrophil functions in vitro and lipopolysaccharide-induced neutrophilic infiltration in vivo","volume":"17","author":"Antoine","year":"2013","journal-title":"Int Immunopharmacol"},{"key":"2021120808183187600_cei12993-bib-0021","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.4049\/jimmunol.0803041","article-title":"Neutrophils sequestered in the liver suppress the proinflammatory response of Kupffer cells to systemic bacterial infection","volume":"183","author":"Holub","year":"2009","journal-title":"J Immunol"},{"key":"2021120808183187600_cei12993-bib-0022","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1136\/gut.50.4.501","article-title":"Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis","volume":"50","author":"Carlson","year":"2002","journal-title":"Gut"},{"key":"2021120808183187600_cei12993-bib-0023","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"2021120808183187600_cei12993-bib-0024","doi-asserted-by":"crossref","first-page":"14983","DOI":"10.1073\/pnas.1206641109","article-title":"Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation","volume":"109","author":"El Kebir","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021120808183187600_cei12993-bib-0025","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrc883","article-title":"The Bcl2 family: regulators of the cellular life-or-death switch","volume":"2","author":"Cory","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"2021120808183187600_cei12993-bib-0026","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/dvg.22844","article-title":"Early development of the neural plate: new roles for apoptosis and for one of its main effectors caspase-3","volume":"53","author":"Juraver-Geslin","year":"2015","journal-title":"Genesis"},{"key":"2021120808183187600_cei12993-bib-0027","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/ard.2006.061507","article-title":"Effects of intra-articular corticosteroids and anti-TNF therapy on neutrophil activation in rheumatoid arthritis","volume":"66","author":"Wittkowski","year":"2007","journal-title":"Ann Rheum Dis"},{"key":"2021120808183187600_cei12993-bib-0028","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nri3399","article-title":"Neutrophil recruitment and function in health and inflammation","volume":"13","author":"Kolaczkowska","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"2021120808183187600_cei12993-bib-0029","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0167-5699(97)01087-6","article-title":"Seeing the wood for the trees: the forgotten role of neutrophils in rheumatoid arthritis","volume":"18","author":"Edwards","year":"1997","journal-title":"Immunol Today"},{"key":"2021120808183187600_cei12993-bib-0030","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/art.1780390703","article-title":"Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis","volume":"39","author":"Paleolog","year":"1996","journal-title":"Arthritis Rheum"},{"key":"2021120808183187600_cei12993-bib-0031","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2021120808183187600_cei12993-bib-0032","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1002\/art.21394","article-title":"A novel mechanism of neutrophil recruitment in a coculture model of the rheumatoid synovium","volume":"52","author":"Lally","year":"2005","journal-title":"Arthritis Rheum"},{"key":"2021120808183187600_cei12993-bib-0033","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1582-4934.2001.tb00152.x","article-title":"Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis","volume":"5","author":"Bostan","year":"2001","journal-title":"J Cell Mol Med"},{"key":"2021120808183187600_cei12993-bib-0034","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S1357-2725(03)00259-0","article-title":"Rheumatoid arthritis: regulation of synovial inflammation","volume":"36","author":"Sweeney","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"key":"2021120808183187600_cei12993-bib-0035","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/ar2370","article-title":"Recent developments in the immunobiology of rheumatoid arthritis","volume":"10","author":"Andersson","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"2021120808183187600_cei12993-bib-0036","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3109\/10715762.2014.886327","article-title":"Myeloperoxidase and its products in synovial fluid of patients with treated or untreated rheumatoid arthritis","volume":"48","author":"Nzeusseu Toukap","year":"2014","journal-title":"Free Radic Res"},{"key":"2021120808183187600_cei12993-bib-0037","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"Pham","year":"2006","journal-title":"Nat Rev Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12993","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/190\/1\/29\/41644276\/cei12993.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/190\/1\/29\/41644276\/cei12993.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T10:22:42Z","timestamp":1719224562000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/190\/1\/29\/6412387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,3]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,7,3]]},"published-print":{"date-parts":[[2017,9,7]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12993","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,10]]},"published":{"date-parts":[[2017,7,3]]}}}