2011 journal article
Enterococcus faecalis Metalloprotease Compromises Epithelial Barrier and Contributes to Intestinal Inflammation
GASTROENTEROLOGY, 141(3), 959–971.
author keywords: IBD; Bacteria-Host Interactions; Bacterial Protease; Intestinal Barrier Function
MeSH headings : Animals; CD4-Positive T-Lymphocytes / physiology; Cadherins / metabolism; Cell Membrane Permeability / physiology; Colitis / etiology; Colitis / metabolism; Colitis / physiopathology; Disease Models, Animal; Enterococcus faecalis / metabolism; Gelatinases / metabolism; Gram-Positive Bacterial Infections / complications; Gram-Positive Bacterial Infections / metabolism; Gram-Positive Bacterial Infections / physiopathology; Interleukin-10 / genetics; Interleukin-10 / metabolism; Intestinal Mucosa / cytology; Intestinal Mucosa / metabolism; Metalloproteases / metabolism; Mice; Mice, Knockout; Mice, Mutant Strains; Tumor Necrosis Factor-alpha / genetics; Tumor Necrosis Factor-alpha / metabolism
TL;DR:
The metalloprotease GelE, produced by commensal strains of E faecalis, contributes to development of chronic intestinal inflammation in mice that are susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) by impairing epithelial barrier integrity.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 6, 2018
BACKGROUND & AIMS Matrix metalloproteases (MMPs) mediate pathogenesis of chronic intestinal inflammation. We characterized the role of the gelatinase (GelE), a metalloprotease from Enterococcus faecalis, in the development of colitis in mice. METHODS Germ-free, interleukin-10-deficient (IL-10(-/-)) mice were monoassociated with the colitogenic E faecalis strain OG1RF and isogenic, GelE-mutant strains. Barrier function was determined by measuring E-cadherin expression, transepithelial electrical resistance (TER), and translocation of permeability markers in colonic epithelial cells and colon segments from IL-10(-/-) and TNF(ΔARE/Wt) mice. GelE specificity was shown with the MMP inhibitor marimastat. RESULTS Histologic analysis (score 0-4) of E faecalis monoassociated IL-10(-/-) mice revealed a significant reduction in colonic tissue inflammation in the absence of bacteria-derived GelE. We identified cleavage sites for GelE in the sequence of recombinant mouse E-cadherin, indicating that it might be degraded by GelE. Experiments with Ussing chambers and purified GelE revealed the loss of barrier function and extracellular E-cadherin in mice susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) before inflammation developed. Colonic epithelial cells had reduced TER and increased translocation of permeability markers after stimulation with GelE from OG1RF or strains of E faecalis isolated from patients with Crohn's disease and ulcerative colitis. CONCLUSIONS The metalloprotease GelE, produced by commensal strains of E faecalis, contributes to development of chronic intestinal inflammation in mice that are susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) by impairing epithelial barrier integrity.