Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

Toxicol Appl Pharmacol. 2012 Sep 15;263(3):296-302. doi: 10.1016/j.taap.2012.07.001. Epub 2012 Jul 10.

Abstract

In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cerebrosides / administration & dosage
  • Cerebrosides / pharmacology*
  • Colitis / drug therapy*
  • Colitis / physiopathology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism
  • Interleukin-10 / blood
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Poly(ADP-ribose) Polymerases / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cerebrosides
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • cerebroside D
  • Interleukin-10
  • Interferon-gamma
  • Dextran Sulfate
  • Poly(ADP-ribose) Polymerases
  • Caspases