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Cathelicidin-BF, a Novel Antimicrobial Peptide from Bungarus fasciatus, Attenuates Disease in a Dextran Sulfate Sodium Model of Colitis.

Abstract
Antimicrobial peptides are molecules of innate immunity. Cathelicidin-BF is the first cathelicidin peptide found in reptiles. However, the immunoregulatory and epithelial barrier protective properties of C-BF have not been reported. Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, can lead to colon cancer, the third most common malignant tumor. The objective is to develop the new found cathelicidin-BF as a therapeutic to patients of ulcerative colitis. The morphology of the colon epithelium was observed by H&E staining; apoptosis index and infiltration of inflammatory cells in colonic epithelium were measured by TUNEL and immunohistochemistry; the expression level of endogenous mCRAMP was analyzed by immunofluorescence; and phosphorylation of the transcription factors c-jun and NF-κB in colon were analyzed by Western blot. Our results showed that the morphology of the colon epithelium in the C-BF+DSS group was improved compared with the DSS group. Apoptosis and infiltration of inflammatory cells in colonic epithelium were also significantly attenuated in the C-BF+DSS group compared with the DSS group, and the expression level of endogenous mCRAMP in the DSS group was significantly higher than other groups. DSS-induced phosphorylation level of c-jun and NF-κB while C-BF effectively inhibited phosphorylation of NF-κB (p65). The barrier protective effect of C-BF was still excellent. In conclusion, C-BF effectively attenuated inflammation and improved disrupted barrier function. Notably, this is the first report to demonstrate that C-BF attenuates DSS-induced UC both through the regulation of intestinal immune and retention of barrier function, and the exact pathway was through NF-κB.
AuthorsHaiwen Zhang, Xi Xia, Feifei Han, Qin Jiang, Yili Rong, Deguang Song, Yizhen Wang
JournalMolecular pharmaceutics (Mol Pharm) Vol. 12 Issue 5 Pg. 1648-61 (May 04 2015) ISSN: 1543-8392 [Electronic] United States
PMID25807257 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • NF-kappa B
  • cathelicidin BF, Bungarus fasciatus
Topics
  • Animals
  • Anti-Infective Agents (therapeutic use)
  • Antimicrobial Cationic Peptides (therapeutic use)
  • Apoptosis (drug effects)
  • Bungarus (metabolism)
  • Cathelicidins (therapeutic use)
  • Colitis (drug therapy)
  • Colon (metabolism)
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B (metabolism)
  • Signal Transduction

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