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SEW2871 Protects From Experimental Colitis Through Reduced Epithelial Cell Apoptosis and Improved Barrier Function in interleukin-10 Gene-Deficient Mice

SEW2871 Protects From Experimental Colitis Through Reduced Epithelial Cell Apoptosis and Improved Barrier Function in interleukin-10 Gene-Deficient Mice

Jianning Dong, Honggang Wang, Jie Zhao, Jing Sun, Tenghui Zhang, Lugen Zuo, Weiming Zhu, Jianfeng Gong, Yi Li, Lili Gu, Jieshou Li

Immunol Res. 2015 Mar;61(3):303-11.

PMID: 25588868

Abstract:

Loss of intestinal epithelial barrier function including typical tight junction changes and epithelial cell apoptosis plays an important role in Crohn's disease. SEW2871, a selective sphingosine-1-phosphate type-1 receptor agonist, has been proven to be efficient in protecting against colitis in IL-10(-/-) mice in our previous study. Here we performed additional studies to investigate whether treatment with SEW2871 was associated with an improved epithelial barrier function in IL-10(-/-) mice. SEW2871 was administered by gavage at a dose of 20 mg/kg/day for 2 weeks to IL-10(-/-) mice. Severity of colitis, CD4+ T cells in colon lamina propria and proinflammatory cytokine productions were evaluated. Furthermore, intestinal permeability, tight junction (occludin and ZO-1) expressions and distributions, as well as epithelial cell apoptosis, were also assessed. SEW2871 treatment attenuated established colitis associated with decreased CD4+ T cells in colon lamina propria and reduced TNF-α and IFN-γ levels. Moreover, enhanced barrier function, which resulted from ameliorated tight junction (occludin and ZO-1) expressions and suppressed epithelial cell apoptosis, was found to contribute to the therapeutic effects. SEW2871 treatment protects from colitis in IL-10(-/-) mice through reduced epithelial cell apoptosis and improved barrier function. Thus, targeting sphingosine-1-phosphate may represent a new therapeutic approach in Crohn's disease.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP256414752	SEW2871		256414-75-2	Price

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