Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019158 (
hepatitis
)
30,205
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
TR6
, a member of the tumor necrosis factor (TNF) receptor superfamily, has recently been shown to bind to Fas ligand (FasL) and inhibit FasL-mediated cell killing in vitro. In the current study, we demonstrate that
TR6
can block the lethal activity of FasL in multiple in vitro systems, and extend this finding to an in vivo model of
hepatitis
. The binding of human
TR6
to human FasL was verified with BIAcore chip technology. Human primary hepatocytes, HT-29 cells and Jurkat cells were assayed for viability to demonstrate
TR6
inhibition of FasL-mediated cytotoxicity in vitro. Human
TR6
was also shown to cross-react with membrane-bound mouse FasL, since the in vitro cytotoxic activity of L929 cells transfected with murine FasL was inhibited in the presence of human
TR6
. In vivo, FasL-induced acute, lethal, fulminant hepatic apoptosis resulting in death within 2 h of intravenous injection into Fas+ mice, but not Fas- MRL/lpr mice. Pretreatment of mice with
TR6
blocked FasL-induced mortality, presumably by attenuating FasL-induced hepatic apoptosis. Thus, in both in vitro and in vivo systems,
TR6
acts as a functional FasL decoy receptor and may be clinically useful in the treatment of
hepatitis
and other diseases associated with FasL-mediated tissue injury.
...
PMID:In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor. 1140 21
