Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in [Cnlp.sup.-/-] mice

Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in [Cnlp.sup.-/-] mice

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 i...

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Bibliographic Details
Published in:Gene therapy Vol. 20; no. 2; pp. 187 - 193
Main Authors: Tai, E.K.K, Wu, W.K.K, Wang, X.J, Wong, H.P.S, Yu, L, Li, Z.J, Lee, C.W, Wong, C.C.M, Yu, J, Sung, J.J.Y, Gallo, R.L, Cho, C.H
Format: Journal Article
Language:English
Published: Nature Publishing Group 01-02-2013
Subjects:
Care and treatment
Gene therapy
Genetic aspects
Peptides
Physiological aspects
Ulcerative colitis
China
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Summary: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.sup.-/-]) mice as a model. [Cnlp.sup.-/-] 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.sup.-/-] mice. Moreover, mucus secretion and mucin gene expression were impaired in [Cnlp.sup.-/-] 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. Gene Therapy (2013) 20, 187-193;doi:10.1038/gt.2012.22; published online 1 March 2012 Keywords: cathelicidin; antimicrobial peptide; mucin; IL-1;TNF; ulcerative colitis
ISSN:0969-7128
1476-5462
DOI:10.1038/gt.2012.22