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Beta-galactosylceramide alters invariant natural killer T cell function and is effective treatment for lupus.

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.
AuthorsSufi R Morshed, Tsuyoshi Takahashi, Paul B Savage, Neeraja Kambham, Samuel Strober
JournalClinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 132 Issue 3 Pg. 321-33 (Sep 2009) ISSN: 1521-7035 [Electronic] United States
PMID19564135 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Antinuclear
  • Antigens, CD1d
  • Ceramides
  • Monosaccharides
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • beta-galactosyl ceramide
  • Interleukin-4
  • Interferon-gamma
Topics
  • Animals
  • Antibodies, Antinuclear (blood)
  • Antigens, CD1d (immunology, metabolism)
  • B-Lymphocytes (drug effects, immunology, metabolism)
  • Ceramides (immunology, metabolism, pharmacology, therapeutic use)
  • Female
  • Interferon-gamma (blood)
  • Interleukin-4 (blood)
  • Kidney (drug effects, pathology)
  • Liver (immunology)
  • Lupus Erythematosus, Systemic (immunology, pathology, therapy)
  • Lupus Nephritis (immunology, pathology, therapy)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Monosaccharides (immunology, metabolism, pharmacology, therapeutic use)
  • Natural Killer T-Cells (drug effects, immunology, metabolism)
  • Proteinuria (pathology, urine)
  • Receptors, Antigen, T-Cell (immunology, metabolism)
  • Receptors, Antigen, T-Cell, alpha-beta (immunology, metabolism)
  • Spleen (immunology)
  • Survival Analysis

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