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Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp−/− mice

Gene Therapy volume 20, pages 187–193 (2013)Cite this article

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Abstract

Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and immune cells. Whether endogenous cathelicidin is protective against ulcerative colitis, however, is unclear. Here we sought to delineate the role of endogenous murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp−/−) mice as a model. Cnlp−/− mice had more severe symptoms and mucosal disruption than the wild-type mice in response to DSS challenge. The tissue levels of interleukin-1β and tumor necrosis factor-α, myeloperoxidase activity and the number of apoptotic cells were increased in the colon of DSS-challenged Cnlp−/− mice. Moreover, mucus secretion and mucin gene expression were impaired in Cnlp−/− mice. All these abnormalities were reversed by the intrarectal administration of mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may protect against ulcerative colitis through modulation of inflammation and mucus secretion.

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Acknowledgements

This work is partially supported by the Hong Kong Research Grants Council (CUHK 7565/06M).

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  1. E K K Tai and W K K Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    E K K Tai, H P S Wong, L Yu, Z J Li, C C M Wong & C H Cho

  2. Department of Medicine & Therapeutics, Institute of Digestive Diseases, The Chinese University of Hong Kong, Hong Kong, China

    W K K Wu, X J Wang, C W Lee, J Yu, J J Y Sung & C H Cho

  3. Faculty of Medicine, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China

    W K K Wu, X J Wang, C W Lee, J Yu, J J Y Sung & C H Cho

  4. Division of Dermatology, University of California, San Diego, CA, USA

    R L Gallo

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  1. E K K Tai
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Correspondence to C H Cho.

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Tai, E., Wu, W., Wang, X. et al. Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp−/− mice. Gene Ther 20, 187–193 (2013). https://doi.org/10.1038/gt.2012.22

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