Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes.
Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes.
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DOI：
10.1016/j.taap.2012.07.001
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发表时间：
2012-09
影响因子：
3.8
通讯作者：
Xue-feng Wu;Xingxin Wu;Wen-jie Guo;Qiong Luo;Yanhong Gu;Yan Shen;R. Tan;Yang Sun;Qiang Xu
中科院分区：
文献类型：
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作者：
Xue-feng Wu;Xingxin Wu;Wen-jie Guo;Qiong Luo;Yanhong Gu;Yan Shen;R. Tan;Yang Sun;Qiang Xu
本论文旨在研究一种神经酰胺类化合物-甘草苷D对小鼠实验性结肠炎的新作用。脑苷脂D可显著降低大鼠体重下降、死亡率，减轻右旋糖酐硫酸钠诱导的结肠炎的大体和镜下表现。该化合物还能浓度依赖性地降低实验性结肠炎小鼠肠组织中TNF-α、IFN-γ和IL-1β的水平，同时显著升高血清中IL-10的水平。脑苷脂D抑制刀豆球蛋白A或抗CD 3+抗CD 28抗体激活的T细胞增殖并诱导其凋亡。该化合物对幼稚淋巴细胞没有表现出影响，但在T细胞活化过程中阻止细胞进入S期和G2/M期。此外，人参皂苷D的处理导致活化的T细胞的凋亡，伴随caspase 3、9、12和PARP的裂解。这些结果表明，对于治疗结肠炎症的新方法，人参皂苷D对活化的T细胞具有多种作用。
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.