{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:04:06Z","timestamp":1776405846514,"version":"3.51.2"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030313542"],"award-info":[{"award-number":["2017A030313542"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571608"],"award-info":[{"award-number":["81571608"]}],"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":["81671568"],"award-info":[{"award-number":["81671568"]}],"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":["81771771"],"award-info":[{"award-number":["81771771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mannan\u2010binding lectin (MBL) acts as a soluble pattern recognition molecule in the innate immune system, which is primarily produced by the liver. MBL deficiency occurs with high frequency in the population and is reported to be associated with susceptibility to several liver diseases. In the present study, we investigated the pathophysiological role of MBL in acetaminophen (APAP)\u2010induced hepatotoxicity. After APAP treatment, MBL\u2010deficient (MBL\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice had significantly higher mortality and aggravated hepatic necrosis as well as elevated serum lactate dehydrogenase and alanine aminotransferase levels compared to control mice. The enhanced hepatotoxicity in MBL\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was associated with increased concentration of APAP toxic metabolisms. Furthermore, we demonstrated here that genetic ablation of MBL resulted in excessive reactive oxygen species (ROS) production and enhanced c\u2010Jun N\u2010terminal kinase (JNK) activation, leading to up\u2010regulated specificity protein 1 (SP1) nuclear expression, thus promoted CYP2E1 hepatic expression and consequently exacerbated APAP\u2010induced liver injury in mice. Importantly, we have validated that MBL protected against APAP toxicity in human HepaRG cells in vitro with the same mechanism. Our study revealed an unexpected function of MBL in drug metabolism, thus providing new insight into the drug\u2010induced liver injury in patients with MBL deficiency.\n                  <\/jats:p>","DOI":"10.1002\/eji.201847830","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T10:23:23Z","timestamp":1549016603000},"page":"564-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mannan\u2010binding lectin attenuates acetaminophen\u2010induced hepatotoxicity by regulating CYP2E1 expression via ROS\u2010dependent JNK\/SP1 pathway"],"prefix":"10.1002","volume":"49","author":[{"given":"Huifang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology Southern Medical University  Guangzhou China"},{"name":"Department of Pathology Anhui Chest Hospital  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Department of Rheumatology\u00a0and Immunology Puyang People's Hospital  Puyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Proteomics Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-9474","authenticated-orcid":false,"given":"Daming","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Proteomics Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000374090"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605143200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.46.65.1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302630200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31816fefb5"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000128859.42696.28"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22578"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37156"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204862200"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.26.16540"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.180321497"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.7147"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.03.015"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/431987"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00789.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03614.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075371"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2015.12.015"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14408"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82358-4"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)68790-3"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23267"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.09.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2001"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.1011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991514"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59755"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.07.006"},{"key":"e_1_2_7_30_1","first-page":"900","article-title":"Fisetin inhibits epidermal growth factor\u2010induced migration of ARPE\u201019 cells by suppression of AKT activation and Sp1\u2010dependent MMP\u20109 expression","volume":"23","author":"Lin H. Y.","year":"2017","journal-title":"Mol. Vis."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072505"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.03.045"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2661"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-2-206"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.649"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.78"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.3.839"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.05.007"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601200RR"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062465"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011031200"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29689"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-09-0881"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511223200"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28486"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct0708278"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-011-9407-0"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201847830","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847830","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201847830","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847830","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T14:26:06Z","timestamp":1694269566000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201847830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/eji.201847830"],"URL":"https:\/\/doi.org\/10.1002\/eji.201847830","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201847830\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847830\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]},"assertion":[{"value":"2018-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}