Blockade of TRAIL pathway ameliorates HBV-induced hepatocyte apoptosis in an acute hepatitis model

Biochem Biophys Res Commun. 2007 Jan 12;352(2):329-34. doi: 10.1016/j.bbrc.2006.11.024. Epub 2006 Nov 14.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may play important roles during hepatitis B virus (HBV) infection. In this study, we used a recombinant human soluble death receptor 5 (sDR5) to explore its effect in a mouse model of HBV-induced acute hepatitis. By measuring blood transaminase activity and hepatocyte apoptosis, we found that sDR5 could alleviate liver damage by blocking TRAIL-induced apoptosis of HBV-transfected hepatocytes. sDR5 injection at 16 mg/kg 24h before HBV transfection was the most effective. Additionally, we showed that sDR5 was equally effective in protecting liver injury as the Stronger Neo-Minophagen C (SNMC), a commonly used drug for patients with liver diseases. Thus, sDR5 represents a potential novel therapeutic drug for patients with fulminant hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects*
  • Disease Models, Animal*
  • Hepatitis B / metabolism*
  • Hepatitis B / pathology*
  • Hepatitis B / prevention & control
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / administration & dosage*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / chemistry
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Signal Transduction / drug effects*
  • Solubility
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Treatment Outcome

Substances

  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand