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1 Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
2 Department of Pathology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
3 ENZO Biochem Inc. New York, New York, USA
* To whom correspondence should be addressed. E-mail: ilan{at}hadassah.org.il.
Concanavalin A induces NKT cell-mediated liver damage. Glucocerebroside (GC) is a naturally
occurring glycolipid. Aims: To determine the effect of GC in a murine model of ConA-induced
hepatitis. Methods: Group A and B mice were treated with GC 2 hours prior to and 2 hours
following administration of Con A, respectively; group C mice were treated with Con A; group
D mice were treated with GC; group E mice did not receive any treatment. Liver damage was
evaluated by serum AST and ALT levels and liver histology. The immune effect of GC was
determined by FACS analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement
of cytokine levels, and western blot analysis for STAT 1, 4, 6 and NF
B expression. The effect
of GC on NKT cell proliferation was assessed in vitro. Results: Serum AST and ALT levels
were markedly reduced in GC-treated group A mice compared to non-treated group C animals,
and histological damage was markedly attenuated in group A. The beneficial effect of GC was
associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum
IFN
levels and decreased STAT1 and STAT6 expression. In vitro, administration of GC led to a
42% decrease of NKT cell proliferation in the presence of dendritic cells, but not in their
absence. IP administered radioactive GC was detected in the liver and bowel. Conclusions:
Administration of GC led to amelioration of Con A hepatitis, associated with an inhibitory effect
on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.
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