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

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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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Acknowledgments

The present study was supported in part by funding from the National Natural Science Foundation of China (Grants 81200263, 81270006 and 81170365) and Jiangsu Provincial Special Program of Medical Sciences, China (BL2012006). This study was also partly supported by the Model Animal Research Center, Nanjing University (Nanjing, China). The authors also want to thank Professor Xiang Gao and Peiliang Shi (Model Animal Research Center of Nanjing University, China) for their excellent technical assistances.

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The authors have no conflicts of interest to declare.

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    Authors and Affiliations

    1. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

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

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    1. Jianning Dong
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    Correspondence to Weiming Zhu.

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    Jianning Dong, Honggang Wang, and Jie Zhao are contributed equally to this work.

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    Dong, J., Wang, H., Zhao, J. et al. SEW2871 protects from experimental colitis through reduced epithelial cell apoptosis and improved barrier function in interleukin-10 gene-deficient mice. Immunol Res 61, 303–311 (2015). https://doi.org/10.1007/s12026-015-8625-5

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