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In the present study, we explored the molecular mechanisms that underlie the anti-inflammatory effect of TQ and its target proteins using lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 and human monocyte-like U937 cells, together with LPS\/D-galactosamine (GalN)-induced acute hepatitis and HCl\/EtOH-induced gastritis mouse models. TQ strongly inhibited the production of nitric oxide (NO) and repressed NO synthase (iNOS), tumor necrosis factor (TNF)-\u03b1, cyclooxygenase (COX)\u22122, interleukin (IL)\u22126, and IL-1\u03b2 expression in LPS-activated RAW264.7 cells. Treatment of LPS\/D-GalN\u2013induced hepatitis and EtOH\/HCl\u2013induced gastritis mouse models with TQ significantly ameliorated disease symptoms. Using luciferase reporter gene assays, we also showed that the nuclear levels of transcription factors and phosphorylation patterns of signaling proteins, activator protein (AP)\u22121, and nuclear factor (NF)-\u03baB pathways were all affected by TQ treatment. Finally, we used additional kinase and luciferase validation assays with interleukin-1 receptor-associated kinase 1 (IRAK1) to show that IRAK1 is directly suppressed by TQ treatment. Together, these findings strongly suggest that the anti-inflammatory actions of TQ are caused by suppression of IRAK-linked AP-1\/NF-\u03baB pathways.<\/jats:p>","DOI":"10.1038\/srep42995","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T10:17:37Z","timestamp":1487585857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities"],"prefix":"10.1038","volume":"7","author":[{"given":"Muhammad Jahangir","family":"Hossen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Seok","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daewon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adithan","family":"Aravinthan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"BFsrep42995_CR1","doi-asserted-by":"crossref","first-page":"S358","DOI":"10.1097\/CCM.0b013e31817e2ffc","volume":"36","author":"CK Murray","year":"2008","unstructured":"Murray, C. 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