Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes.
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.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Xue-Feng
XF
Wu
Xing-Xin
XX
Wu
Wen-Jie
WJ
Guo
Qiong
Q
Luo
Yan-Hong
YH
Gu
Yan
Y
Shen
Ren-Xiang
RX
Tan
Yang
Y
Sun
Qiang
Q
Xu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002554:Cerebrosides / Q000008:administration & dosage / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000503:physiopathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D002554:Cerebrosides; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C438630:cerebroside D; D016753:Interleukin-10; D007371:Interferon-gamma; D016264:Dextran Sulfate; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases