OBJECTIVE: High-mobility group box-1 (HMGB1) is identified as an extracellularly released mediator of inflammation. In this study, specific monoclonal anti-HMGB1 antibody was administered to rats with acute on chronic liver failure (ACLF) in order to evaluate the therapeutic efficacy of HMGB1 blockade. METHODS: All animals were randomly divided into control group, model group and anti-HMGB1 antibody group. The changes in liver histology and apoptosis of liver tissue were detected by H&E staining and TUNEL assay, respectively. The serum levels of alanine aminotransferase (ALT), endotoxin, HMGB1, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were examined. The hepatic levels of HMGB1, caspase3, Toll-like receptor 4 (TLR4) and p65 subunit of NF-κB (P65) were also determined. RESULTS: Changes in liver pathology and liver cell apoptosis were greatly attenuated in the anti-HMGB1 antibody group compared with the model group. The serum levels of ALT, endotoxin, TNF-α, IFN-γ and HMGB1 were also decreased in the anti-HMGB1 antibody group. Furthermore, the hepatic levels of HMGB1, TLR4, caspase3 and P65 were also down-regulated by HMGB1 blockade. CONCLUSION: Blockade of HMGB1 can confer a protective effect against ACLF in rats, even 24 h after induction of ACLF. The protective effect of HMGB1 blockade is associated with interactions of HMGB1 with the TLR4 signaling pathway and cytokine production.
OBJECTIVE:High-mobility group box-1 (HMGB1) is identified as an extracellularly released mediator of inflammation. In this study, specific monoclonal anti-HMGB1 antibody was administered to rats with acute on chronic liver failure (ACLF) in order to evaluate the therapeutic efficacy of HMGB1 blockade. METHODS: All animals were randomly divided into control group, model group and anti-HMGB1 antibody group. The changes in liver histology and apoptosis of liver tissue were detected by H&E staining and TUNEL assay, respectively. The serum levels of alanine aminotransferase (ALT), endotoxin, HMGB1, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were examined. The hepatic levels of HMGB1, caspase3, Toll-like receptor 4 (TLR4) and p65 subunit of NF-κB (P65) were also determined. RESULTS: Changes in liver pathology and liver cell apoptosis were greatly attenuated in the anti-HMGB1 antibody group compared with the model group. The serum levels of ALT, endotoxin, TNF-α, IFN-γ and HMGB1 were also decreased in the anti-HMGB1 antibody group. Furthermore, the hepatic levels of HMGB1, TLR4, caspase3 and P65 were also down-regulated by HMGB1 blockade. CONCLUSION: Blockade of HMGB1 can confer a protective effect against ACLF in rats, even 24 h after induction of ACLF. The protective effect of HMGB1 blockade is associated with interactions of HMGB1 with the TLR4 signaling pathway and cytokine production.
Authors: Beatriz Rendon-Mitchell; Mahendar Ochani; Jianhua Li; Jialian Han; Hong Wang; Huan Yang; Seenu Susarla; Christopher Czura; Robert A Mitchell; Guoqian Chen; Andrew E Sama; Kevin J Tracey; Haichao Wang Journal: J Immunol Date: 2003-04-01 Impact factor: 5.422
Authors: A Poltorak; X He; I Smirnova; M Y Liu; C Van Huffel; X Du; D Birdwell; E Alejos; M Silva; C Galanos; M Freudenberg; P Ricciardi-Castagnoli; B Layton; B Beutler Journal: Science Date: 1998-12-11 Impact factor: 47.728
Authors: Huan Yang; Mahendar Ochani; Jianhua Li; Xiaoling Qiang; Mahira Tanovic; Helena E Harris; Srinivas M Susarla; Luis Ulloa; Hong Wang; Robert DiRaimo; Christopher J Czura; Haichao Wang; Jesse Roth; H Shaw Warren; Mitchell P Fink; Matthew J Fenton; Ulf Andersson; Kevin J Tracey Journal: Proc Natl Acad Sci U S A Date: 2003-12-26 Impact factor: 11.205
Authors: Evangelos Triantafyllou; Kevin J Woollard; Mark J W McPhail; Charalambos G Antoniades; Lucia A Possamai Journal: Front Immunol Date: 2018-12-14 Impact factor: 7.561