Neutralization of tumor necrosis factor abrogates hepatic failure induced by alpha-galactosylceramide without attenuating its antitumor effect in aged mice.
J Hepatol
; 43(4): 670-8, 2005 Oct.
Article
in En
| MEDLINE
| ID: mdl-15922476
ABSTRACT
BACKGROUND/AIMS:
The functions of mouse liver NK1.1+ T (NKT) cells stimulated with alpha-galactosylceramide (alpha-GalCer) are enhanced age dependently, and the antitumor and anti-metastatic effect in the liver is dependent on IFN-gamma. However, hepatic injury is independent of IFN-gamma and Fas/Fas-ligand dependent. The aim of this study is to investigate how tumor necrosis factor is involved in the alpha-GalCer-mediated immune phenomena.METHODS:
C57BL/6 mice were intraperitoneally treated with anti-TNF antibody 1 h before alpha-GalCer injection, and Fas-ligand expression of NKT cells, the serum ALT levels and histopathological findings of the liver, kidney and lung and mortality after alpha-GalCer injection were evaluated. IFN-gamma production and antitumor immunity in the liver after the intravenous injection of EL-4 cells were also assessed.RESULTS:
Serum TNF levels after alpha-GalCer injection increased age dependently in mice. Anti-TNF Ab reduced Fas-ligand (Fas-L) expression of NKT cells while it completely inhibited organ injuries induced by alpha-GalCer and thereby reduced the mortality of old mice, whereas it did not affect the IFN-gamma production from NKT cells, the antitumor immunity in the liver nor the mouse survival after EL-4 injection.CONCLUSIONS:
NKT cells activated by alpha-galactosylceramide participated in either antitumor immunity or hepatic injury using IFN-gamma and TNF/Fas-L, respectively.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Necrosis Factor-alpha
/
Liver Failure
/
Galactosylceramides
Limits:
Animals
Language:
En
Journal:
J Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2005
Document type:
Article
Affiliation country:
Japan