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Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function

Cellular & Molecular Immunology volume 13, pages 110–118 (2016)Cite this article

Abstract

The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 (Trek1) in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic (Clostridium butyricum) restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.

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Acknowledgements

This study was supported by grants from the 973 Program (#2011CB512006) of China, The Natural Science Foundation of SZU (No. 000004), the Innovation of Science and Technology Commission of Shenzhen Municipality (JCYJ20120613172559904) and The Natural Science Foundation of China (Nos. 30871752 and 81373176).

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Author notes

  1. Huang Huang and Jiang-Qi Liu: These authors equally contributed to this work.

  2. Dr PC Yang, Dr PY Zheng and Dr ZG Liu, Room 722 of the Medical School Building; 3688 Nanhai Ave., Shenzhen, 518060, China. E-mail: pcy2356@szu.edu.cn

Authors and Affiliations

  1. Department of Gastroenterology, the Second Hospital, Zhengzhou University, Zhengzhou, China

    Huang Huang, Yong Yu & Peng-Yuan Zheng

  2. ENT Institute, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen, China

    Jiang-Qi Liu, Li-Hua Mo, Zhi-Gang Liu & Ping-Chang Yang

  3. ENT Hospital, Longgang Central Hospital, Shenzhen, China

    Jiang-Qi Liu

  4. Brain Body Institute, McMaster University, Hamilton, ON, Canada

    Jiang-Qi Liu, Rong-Ti Ge, Huan-Ping Zhang & Ping-Chang Yang

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  1. Huang Huang
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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Huang, H., Liu, JQ., Yu, Y. et al. Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function. Cell Mol Immunol 13, 110–118 (2016). https://doi.org/10.1038/cmi.2014.137

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