title: Inhibitions of NF-κB and TNF-α result in differential effects in rats with acute on chronic liver failure induced by d-Gal and LPS.
abstract: In this study, we induced an acute-on-chronic liver failure (ACLF) model by human serum albumin (HSA), D-galactosamine (D-Gal) and lipopolysaccharide (LPS) in rats. Anti-TNF-α polyclonal antibody (as TNF-α inhibitor) and pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor) were used to treat the liver failure animals, respectively. The results showed that TNF-α inhibition was beneficial, but NF-κB inhibition failed to protect the rats in ACLF. However, HMGB1 levels, cytokine production and activation of TLR4-NF-κB signaling pathway were all suppressed by both TNF-α and NF-κB inhibition. In order to verify the effect of PDTC on inflammatory response, we further explored its effect in vitro. Anti-inflammatory activity of PDTC was proved in U937 cell line. To conclude, both inhibitions of TNF-α and NF-κB are able to suppress the activation of TLR4 and NF-κB signaling pathway. However, NF-κB inhibition with PDTC failed to protect the rats in ACLF induced by D-Gal and LPS.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Han
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005688:Galactosamine; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013859:Thiocarbamates / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D008070:Lipopolysaccharides; D011759:Pyrrolidines; C498144:Rela protein, mouse; D013859:Thiocarbamates; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D005688:Galactosamine