title: Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1.
abstract: High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release.
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China ; Wenzhou Key Laboratory of Hepatology Wenzhou 325000, Zhejiang, P. R. China ; Hepatology Institute of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
authors.forename: Nai-Bin
authors.initials: NB
authors.lastname: Yang
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China ; Wenzhou Key Laboratory of Hepatology Wenzhou 325000, Zhejiang, P. R. China ; Hepatology Institute of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
authors.forename: Shun-Lan
authors.initials: SL
authors.lastname: Ni
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China ; Wenzhou Key Laboratory of Hepatology Wenzhou 325000, Zhejiang, P. R. China ; Hepatology Institute of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China ; Wenzhou Key Laboratory of Hepatology Wenzhou 325000, Zhejiang, P. R. China ; Hepatology Institute of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University 108 Wansong Road, Ruian 325200, Zhejiang, China.
authors.forename: Dan-Ping
authors.initials: DP
authors.lastname: Hu
authors.affiliation: Department of Infection Diseases, The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China ; Wenzhou Key Laboratory of Hepatology Wenzhou 325000, Zhejiang, P. R. China ; Hepatology Institute of Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
authors.forename: Ming-Qin
authors.initials: MQ
authors.lastname: Lu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004361:Drug Tolerance; D024243:HMGB1 Protein / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha
keywords: Endotoxin tolerance; JAK/STAT1 signaling; acute liver failure; high mobility group box 1; lipopolysaccharide (LPS)