Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders.
BACKGROUND
beta-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes.


OBJECTIVE
To determine whether beta-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells.


METHODS
The immunological effect of beta-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression.


RESULTS
Administration of beta-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in beta-glucosylceramide-treated mice solely in the HCC model. The effect of beta-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon gamma levels in the colitis model, whereas an opposite effect was noted in the HCC model.


CONCLUSIONS
beta-glucosylceramide alleviates immunologically incongruous disorders and may be associated with "fine tuning" of immune responses, by changes in plasticity of NKT lymphocytes.
Zigmond
E
E
Liver Unit, Department of Medicine, Hebrew University Hadassah Medical Center, PO Box 12000, Jerusalem, Israel IL-91120.
Preston
S
S
Pappo
O
O
Lalazar
G
G
Margalit
M
M
Shalev
Z
Z
Zolotarov
L
L
Friedman
D
D
Alper
R
R
Ilan
Y
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005963:Glucosylceramides / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050791:STAT Transcription Factors / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D005963:Glucosylceramides; D050791:STAT Transcription Factors; D016753:Interleukin-10; D007371:Interferon-gamma