4.6 Article

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

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 263, Issue 3, Pages 296-302

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2012.07.001

Keywords

Cerebroside D; Inflammatory bowel disease; Activated T cells

Funding

  1. National Natural Science Foundation of China [30973546, 30973920]
  2. NSFC [81121062]
  3. Natural Science Foundation of Jiangsu Province [BK2011053]
  4. 'Production-Science-Research' Forward-looking Project of Jiangsu Province [BY2010138]
  5. National Science & Technology Major Project [2012ZX09304-001]

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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-alpha, IFN-gamma and IL-1 beta 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. (C) 2012 Elsevier Inc. All rights reserved.

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