{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:43:19Z","timestamp":1790476999883,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"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","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hepatic sinusoidal obstruction syndrome (HSOS) causes considerable morbidity and mortality in clinic. Up to now, the molecular mechanisms involved in the development of HSOS still remain unclear. Here, we report that hepatic inflammation initiated by damage-associated molecular patterns (DAMPs) plays a critical role in the development of HSOS. Monocrotaline (MCT) belongs to pyrrolizidine alkaloids. Monocrotaline-induced HSOS in mice and rats was evidenced by the increased serum alanine\/aspartate aminotransferase (ALT\/AST) activities, the elevated hepatic metalloproteinase 9 (MMP9) expression, and results from liver histological evaluation and scanning electron microscope observation. However, MCT-induced HSOS was markedly attenuated in myeloid differentiation primary response gene 88 (MyD88), TIR-domain-containing adapter-inducing interferon-\u03b2 (TRIF) and toll like receptor 4 (TLR4) knock-out mice. Monocrotaline increased liver myeloperoxidase activity, serum contents of proinflammatory cytokines, hepatic aggregation of immune cells, and nuclear accumulation of nuclear factor \u03baB (NF\u03baB). However, these inflammatory responses induced by MCT were all diminished in MyD88, TRIF, and TLR4 knock-out mice. Monocrotaline elevated serum contents of DAMPs including high mobility group box 1 (HMGB1) and heat shock protein 60 (HSP60) both in mice and in rats. HSOS was markedly exacerbated and serum contents of HMGB1 and HSP60 were elevated in nuclear factor erythroid 2-related factor 2 (Nrf2) knock-out mice treated with MCT. Our findings indicate that hepatic inflammatory injury mediated by DAMPs-initiated TLR4-MyD88\/TRIF-NF\u03baB inflammatory signal pathway plays an important role in HSOS development.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz193","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T07:39:21Z","timestamp":1566805161000},"page":"385-397","source":"Crossref","is-referenced-by-count":25,"title":["Liver Inflammatory Injury Initiated by DAMPs-TLR4-MyD88\/TRIF-NF\u03baB Signaling Pathway Is Involved in Monocrotaline-Induced HSOS"],"prefix":"10.1093","volume":"172","author":[{"given":"Zhenlin","family":"Huang","sequence":"first","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minwei","family":"Chen","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjuan","family":"Wei","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Wu","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengtao","family":"Wang","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-2626","authenticated-orcid":false,"given":"Lili","family":"Ji","sequence":"additional","affiliation":[{"name":"The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"key":"2019112509003194400_kfz193-B1","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1182\/blood.V85.11.3005.bloodjournal85113005","article-title":"The syndrome of hepatic veno-occlusive disease after marrow transplantation","volume":"85","author":"Bearman","year":"1995","journal-title":"Blood"},{"key":"2019112509003194400_kfz193-B2","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.4049\/jimmunol.169.11.6141","article-title":"Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells: Superiority of HSP60","volume":"169","author":"Bethke","year":"2002","journal-title":"J. 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