Cathelicidin, an
antimicrobial peptide of the innate immune system, modulates microbial growth, wound healing, and
inflammation. However, its association with
inflammatory bowel diseases (IBDs) is unknown. Our objective was to determine whether
cathelicidin would exert a modulatory effect on the progression of IBD and, if so, investigate the mechanism of action through which this effect occurred. We evaluated the potential for a synthetic
cathelicidin, the mouse
cathelin-related antimicrobial peptide (mCRAMP), to prevent the initiation and promote the healing of lesions from inflammatory
colitis that was experimentally induced in mice with
dextran sulfate sodium (DSS). During the experiment, mCRAMP was given: (i) as a parallel treatment starting together with 3% DSS feeding, and (ii) as a posttreatment starting 7 days after 3% DSS feeding. The
body weight, fecal microflora populations, clinical symptoms, and histologic findings of colonic tissues were measured. Relative gene expression of
mucins (MUC1, MUC2, MUC3, and MUC4) in colonic tissues was determined by real-time polymerase chain reaction. Intrarectal administration of mCRAMP ameliorated DSS-induced
colitis with negligible effects on mucosal healing. The
peptide also significantly reduced the increased number of fecal microflora in
colitis animals. It reversed the decline of colonic mucus thickness during
colitis through upregulation of the expression of
mucin genes. Treatment with mCRAMP also prevented
colitis development by suppressing the induction of apoptosis by DSS. The current study demonstrates for the first time that intrarectal administration of
cathelicidin may be a novel therapeutic option for IBDs.