{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:30:37Z","timestamp":1788543037224,"version":"build-2803163510"},"reference-count":32,"publisher":"Canadian Science Publishing","issue":"11","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p> Brd4 protein is an important epigenetic regulator involved in the process of inflammatory cytokine production in many diseases. However, whether and how Brd4 participates in the process of wear-particle-induced inflammation remain unclear. This study aimed to investigate the potential role of Brd4 in titanium (Ti) particle-induced inflammatory cytokine production in mouse macrophage RAW264.7 cells. Our experiment detected Brd4 expressed in both normal synovium and periprosthetic osteolysis interface membrane, but the expression increased in the interface membrane as compared with that in normal synovium. Treatment with Ti particles significantly increased TNF-\u03b1, IL-6, and IL-1\u03b2 production in RAW264.7 cells, which was inhibited by JQ1 or Brd4-siRNA. Ti particles enhanced the expression of Brd4, which was abrogated by JQ1. Ti particles enhanced NF-\u03baB p65 and IKK phosphorylation and attenuated I\u03baB\u03b1 protein expression, which were abrogated by JQ1. Co-immunoprecipitation analysis indicated that Ti particles promoted the binding of Brd4 to acetylated NF-\u03baB p65 (lysine-310), which was also abrogated in JQ1-treated RAW264.7 cells. In conclusion, Brd4 expression increases in interface membrane and Brd4 participates in the production of pro-inflammatory cytokines induced by Ti particles via promoting the activation of NF-\u03baB signaling and binding to acetylated NF-\u03baB p65 (lysine-310) in mouse macrophages. <\/jats:p>","DOI":"10.1139\/cjpp-2019-0142","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T21:35:45Z","timestamp":1563831345000},"page":"1028-1034","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of Brd4 in the production of inflammatory cytokines in mouse macrophages treated with titanium particles"],"prefix":"10.1139","volume":"97","author":[{"given":"Yuanzhong","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Qingdao Haici Medical Group, Qingdao, Shandong, 266000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266061, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.05.013"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202838"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.03.044"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.02.096"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01026"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1177\/1753425912451779"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines6010016"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01365-08"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13657"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.04.009"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.06.009"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.09.006"},{"issue":"1","key":"refg13\/ref13","first-page":"1","volume":"79","author":"Jiang Y.","year":"2013","journal-title":"Acta Orthop. 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