Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

Enterohemorrhagic Escherichia coli*/drug effects ; Enterohemorrhagic Escherichia coli*/physiology; Cathelicidins/*pharmacology ; Epithelial Cells/*drug effects ; Escherichia coli Infections/*drug therapy ; Intestines/*drug effects; Animals ; Cathelicidins/therapeutic use ; Colitis/drug therapy ; Colon/cytology ; Colon/immunology ; Colon/microbiology ; Epithelial Cells/immunology ; Epithelial Cells/microbiology ; Escherichia coli Infections/immunology ; Escherichia coli Infections/microbiology ; Escherichia coli Infections/physiopathology ; Interleukin-6/biosynthesis ; Interleukin-6/immunology ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; Intestinal Mucosa/microbiology ; Intestines/immunology ; Intestines/microbiology ; Intestines/physiology ; Mice ; Microbiota/drug effects ; Mucin-2/metabolism ; Neuropeptides/metabolism ; Trefoil Factor-3/genetics ; rac1 GTP-Binding Protein/metabolism

Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. Cathelicidin peptides suppress intestinal inflammation and improve intestinal epithelial barrier function independently of their antimicrobial activity. In this study, we investigated the effects of Cathelicidin-WA (CWA) on intestinal epithelial barrier function, as well as the underlying mechanism, by using enterohemorrhagic Escherichia coli (EHEC)-infected mice and intestinal epithelial cells. The results showed that CWA attenuated EHEC-induced clinical symptoms and intestinal colitis, as did enrofloxacin (Enro). CWA decreased IL-6 production in the serum, jejunum, and colon of EHEC-infected mice. Additionally, CWA alleviated the EHEC-induced disruption of mucin-2 and goblet cells in the intestine. Interestingly, CWA increased the mucus layer thickness, which was associated with increasing expression of trefoil factor 3, in the jejunum of EHEC-infected mice. CWA increased the expression of tight junction proteins in the jejunum of EHEC-infected mice. Using intestinal epithelial cells and a Rac1 inhibitor in vitro, we demonstrated that the CWA-mediated increases in the tight junction proteins might depend on the Rac1 pathway. Furthermore, CWA improved the microbiota and short-chain fatty acid concentrations in the cecum of EHEC-infected mice. Although Enro and CWA had similar effects on intestinal inflammation, CWA was superior to Enro with regard to improving intestinal epithelial barrier and microbiota in the intestine. In conclusion, CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases.
(Copyright © 2017 by The American Association of Immunologists, Inc.)

0 (Cathelicidins)
0 (Interleukin-6)
0 (Mucin-2)
0 (Neuropeptides)
0 (Rac1 protein, mouse)
0 (Tff3 protein, mouse)
0 (Trefoil Factor-3)
0 (interleukin-6, mouse)
EC 3.6.5.2 (rac1 GTP-Binding Protein)

Date Created: 20170108 Date Completed: 20170828 Latest Revision: 20180126

20231215

10.4049/jimmunol.1601221

28062699