Acute liver injury attenuation of a novel recombinant sTNFR through blocking hepatic apoptosis. (June 2015)

• Record Type: Journal Article
• Authors: Luo, Mansheng; Zhao, Ai; Li, Jinlong; Chen, Yueping; Tian, Dandan; Wang, Caihong; Hu, Zhiming; Gao, Jimin
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 37:Number 3(2015:Jun.)
• Page Start: 295
• Page End: 300
• Publication Date: 2015-06
• Subjects: Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2015.1035390
• Languages: English
• ISSNs: 0892-3973

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context</italic>: Tumor necrosis factor (TNF) α plays a key role in acute liver injury (ALI) induced by injection of <sc>d</sc>-galactosamine (D-Gal)/lipopolysaccharide (LPS). A novel recombinant trimeric sTNFRII, sTNFRII-gAD, has been tested to be effective in ameliorating ALI, when administered prior to ALI establishment. This study aims to validate the protective effect of sTNFRII-gAD when given after ALI setup and further explore its effect on hepatic apoptosis.</p> <p> <italic>Materials and methods</italic>: The treatments were carried out concomitantly with ALI establishment with clinically approved sTNFRII-Fc (the dimeric sTNFRII) as a positive control. Lethality, liver weight, and serum alanine transaminase were measured, and histological analysis was performed to evaluate liver injury induced by D-Gal/LPS. Additionally, Terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) and Western blot analyses of caspase-3 were used to examine hepatocellular apoptosis.</p> <p> <italic>Results</italic>: sTNFRII-gAD given after D-Gal/LPS injection turned out to attenuate animal mortality significantly (<italic>p</italic> < 0.01), and had better hepatic protection. In terms of apoptosis, both sTNFRII-gAD and sTNFRII-Fc displayed noticeable improvement of apoptosis evidenced by dramatic decline of active caspase-3 compared to the control group.</p> <p> <italic>Conclusions</italic>: The results demonstrated that sTNFRII-gAD therapeutically diminished the lethality induced by D-Gal/LPS, possibly through blocking hepatic apoptosis initiated by TNFα. Of note, sTNFRII-gAD was superior to sTNFRII-Fc in some respects, indicating a promising alternative for the therapeutic strategy against the diseases associated with excessive TNFα.</p> </abstract>