Abstract
NZB/W female mice spontaneously develop systemic lupus, an autoantibody mediated disease associated with immune complex glomerulonephritis. Natural killer (NK) T cells augment anti-dsDNA antibody secretion by NZB/W B cells in vitro, and blocking NKT cell activation in vivo with anti-CD1 mAb ameliorates lupus disease activity. In the current study, we show that beta-galactosylceramide reduces the in vivo induction of serum IFN-gamma and/or IL-4 by the potent NKT cell agonist alpha-galactosylceramide and reduces NKT cell helper activity for IgG secretion. Treatment of NZB/W mice with the beta-galactosylceramide ameliorated lupus disease activity as judged by improvement in proteinuria, renal histopathology, IgG anti-dsDNA antibody formation, and survival. In conclusion, beta-galactosylceramide, a glycolipid that reduces the cytokine secretion induced by a potent NKT cell agonist ameliorates lupus in NZB/W mice.
MeSH terms
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Animals
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Antibodies, Antinuclear / blood
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Antigens, CD1d / immunology
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Antigens, CD1d / metabolism
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Ceramides / immunology
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Ceramides / metabolism
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Ceramides / pharmacology*
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Ceramides / therapeutic use*
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Female
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Interferon-gamma / blood
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Interleukin-4 / blood
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Kidney / drug effects
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Kidney / pathology
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Liver / immunology
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / pathology
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Lupus Erythematosus, Systemic / therapy*
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Lupus Nephritis / immunology
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Lupus Nephritis / pathology
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Lupus Nephritis / therapy
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Mice
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Mice, Inbred C57BL
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Mice, Inbred NZB
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Monosaccharides / immunology
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Monosaccharides / metabolism
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Monosaccharides / pharmacology*
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Monosaccharides / therapeutic use*
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Natural Killer T-Cells / drug effects
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism
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Proteinuria / pathology
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Proteinuria / urine
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Spleen / immunology
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Survival Analysis
Substances
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Antibodies, Antinuclear
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Antigens, CD1d
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Ceramides
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Monosaccharides
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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beta-galactosyl ceramide
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Interleukin-4
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Interferon-gamma