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Immunologic Research
Erschienen in: Immunologic Research 3/2015

01.03.2015

SEW2871 protects from experimental colitis through reduced epithelial cell apoptosis and improved barrier function in interleukin-10 gene-deficient mice

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

Erschienen in: Immunologic Research | Ausgabe 3/2015

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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.
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Metadaten
Titel
SEW2871 protects from experimental colitis through reduced epithelial cell apoptosis and improved barrier function in interleukin-10 gene-deficient mice
verfasst von
Jianning Dong
Honggang Wang
Jie Zhao
Jing Sun
Tenghui Zhang
Lugen Zuo
Weiming Zhu
Jianfeng Gong
Yi Li
Lili Gu
Jieshou Li
Publikationsdatum
01.03.2015
Verlag
Springer US
Erschienen in
Immunologic Research / Ausgabe 3/2015
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-015-8625-5

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