title: Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp(-/-) mice.
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.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: E K K
authors.initials: EK
authors.lastname: Tai
authors.forename: W K K
authors.initials: WK
authors.lastname: Wu
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
authors.forename: H P S
authors.initials: HP
authors.lastname: Wong
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Li
authors.forename: C W
authors.initials: CW
authors.lastname: Lee
authors.forename: C C M
authors.initials: CC
authors.lastname: Wong
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: J J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: R L
authors.initials: RL
authors.lastname: Gallo
authors.forename: C H
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D017209:Apoptosis; D003093:Colitis, Ulcerative / Q000235:genetics / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D053583:Interleukin-1beta; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D054804:Cathelicidins