|  Help  |  About  |  Contact Us

Publication : Genetic determinants of lipopolysaccharide and D-galactosamine-mediated hepatocellular apoptosis and lethality.

First Author  Oberholzer A Year  2001
Journal  J Endotoxin Res Volume  7
Issue  5 Pages  375-80
PubMed ID  11753206 Mgi Jnum  J:117350
Mgi Id  MGI:3696290 Citation  Oberholzer A, et al. (2001) Genetic determinants of lipopolysaccharide and D-galactosamine-mediated hepatocellular apoptosis and lethality. J Endotoxin Res 7(5):375-80
abstractText  Lipopolysaccharide and D-galactosamine induced lethality and apoptotic liver injury is dependent upon endogenously produced TNF-alpha. Unlike the response to high dose lipopolysaccharide alone, death in this model is a direct result of hepatocyte apoptosis. In a series of recent studies, we have demonstrated that mortality and hepatic injury following lipopolysaccharide administration in D-galactosamine-sensitized mice is dependent upon secreted 17 kDa TNF-alpha acting primarily through the p55 TNF receptor. Transgenic mice expressing null forms of TNF-alpha, the p55 receptor, or expressing only a cell-associated form of TNF-alpha exhibited no mortality and only modest liver injury when challenged with 8 mg of D-galactosamine and 100 ng of lipopolysaccharide. Although Fas ligand expression is increased in the liver, it appeared to play no significant role in outcome, since mice expressing a mutant form of Fas ligand are still sensitive to LPS- and D-galactosamine-induced lethality. Finally, we have seen significant variation in LPS- and D-galactosamine-mediated lethality among different strains of mice. The non-obese diabetic or NOD mouse is highly resistant to LPS-and D-galactosamine-induced lethality, and this appears to be secondary to a post-receptor defect in p55 TNF receptor signaling. The studies confirm an essential role for TNF-alpha and p55 TNF receptor signaling in the hepatocyte apoptosis and lethality associated with lipopolysaccharide and D-galactosamine administration.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

8 Bio Entities

Trail: Publication

0 Expression