{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:07:23Z","timestamp":1773979643211,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81200282"],"award-info":[{"award-number":["81200282"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470834"],"award-info":[{"award-number":["81470834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanisms of macrophages\/monocytes in autoimmune hepatitis (AIH) remain unclear. We investigated the role of receptor\u2010interacting protein kinase 3 (RIP3), a key inflammatory signal adapter, in macrophage\/monocyte activation in AIH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver tissues and monocytes from patients were collected to evaluate the relationship between macrophage activation and RIP3 by double\u2010immunofluorescence and Western blotting. RAW264.7 macrophages were used to study the regulation of RIP3 signaling on inflammatory cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to the hepatic cyst, the majority of accumulated macrophages expressed RIP3 in AIH liver tissues. Moreover, RIP3 expression of monocytes was correlated with the levels of serum hepatic enzyme in AIH. Furthermore, RIP3 signaling was activated by lipopolysaccharide in RAW264.7 macrophages, which was accompanied with upregulated interleukin (IL)\u20101\u03b2, IL\u20106, and IL\u201010 and downregulated IL\u20104 and transforming growth factor\u2010\u03b2. Notably, necrostatin\u20101, the specific inhibitor of the RIP3 signaling pathway, and 6\u2010thioguanine (6\u2010TG), the active metabolite of azathioprine, predominantly reduced IL\u20106 production compared to other cytokines. Moreover, the gene level of IL\u20106 was dramatically increased in AIH liver tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>RIP3 signaling is involved in macrophage\/monocyte activation in AIH and mediates IL\u20106 production, and is a novel molecular mechanism of 6\u2010TG, indicating that it might be a promising therapeutic target for AIH treatment.<\/jats:p><\/jats:sec>","DOI":"10.1177\/2050640618756124","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T12:48:09Z","timestamp":1516884489000},"page":"719-728","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Receptor\u2010interacting protein kinase 3 mediates macrophage\/monocyte activation in autoimmune hepatitis and regulates interleukin\u20106 production"],"prefix":"10.1002","volume":"6","author":[{"given":"Jun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathasha","family":"Karunaratna","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bangmao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6]]},"reference":[{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23584"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22306"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991511"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28418"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.003"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25711"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22914"},{"key":"e_1_2_11_9_2","first-page":"325","article-title":"Histologic features in autoimmune hepatitis","volume":"27","author":"Dienes HP","year":"1989","journal-title":"Z Gastroenterol"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199506000-00010"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(02)00022-3"},{"key":"e_1_2_11_12_2","first-page":"247","article-title":"Characterization of the mononuclear cell infiltrate in piecemeal necrosis","volume":"50","author":"Alexander G","year":"1984","journal-title":"Lab Invest"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112248"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.003"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2013.12.013"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.037"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.016"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116302108"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.126"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12068"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.04.015"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01016.x"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22322"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.1.1.1"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040391"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.05.004"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60453-5"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.09.034"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.012"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26583"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02220605"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb35897.x"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318384"}],"updated-by":[{"DOI":"10.1177\/2050640618793759","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T00:00:00Z","timestamp":1533859200000}}],"container-title":["United European Gastroenterology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/2050640618756124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1177\/2050640618756124","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/2050640618756124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T09:59:40Z","timestamp":1693735180000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1177\/2050640618756124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1177\/2050640618756124"],"URL":"https:\/\/doi.org\/10.1177\/2050640618756124","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1177\/2050640618793759","asserted-by":"object"}]},"ISSN":["2050-6406","2050-6414"],"issn-type":[{"value":"2050-6406","type":"print"},{"value":"2050-6414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6]]}}}