Unknown

Dataset Information

0

Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers.


ABSTRACT: Intestinal pathogens use the host's excessive inflammatory cytokine response, designed to eliminate dangerous bacteria, to disrupt epithelial gut wall integrity and promote their tissue invasion. We sought to develop a non-antibiotic-based approach to prevent this injury. Molecular docking studies suggested that glycosylated dendrimers block the TLR4-MD-2-LPS complex, and a 13.6 kDa polyamidoamine (PAMAM) dendrimer glucosamine (DG) reduced the induction of human monocyte interleukin (IL)-6 by Gram-negative bacteria. In a rabbit model of shigellosis, PAMAM-DG prevented epithelial gut wall damage and intestinal villous destruction, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. Computational modelling studies identified a 3.3 kDa polypropyletherimine (PETIM)-DG as the smallest likely bioactive molecule. In human monocytes, high purity PETIM-DG potently inhibited Shigella Lipid A-induced IL-6 expression. In rabbits, PETIM-DG prevented Shigella-induced epithelial gut wall damage, reduced local IL-6 and IL-8 expression, and minimized bacterial invasion. There was no change in ?-defensin, IL-10, interferon-?, transforming growth factor-?, CD3 or FoxP3 expression. Small and orally delivered DG could be useful for preventing gut wall tissue damage in a wide spectrum of infectious diarrhoeal diseases.

SUBMITTER: Teo I 

PROVIDER: S-EPMC3491821 | BioStudies | 2012-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC6938980 | BioStudies
2020-01-01 | S-EPMC6974573 | BioStudies
1000-01-01 | S-EPMC3101704 | BioStudies
1000-01-01 | S-EPMC3926043 | BioStudies
2014-01-01 | S-EPMC4198040 | BioStudies
2018-01-01 | S-EPMC5755796 | BioStudies
2014-01-01 | S-EPMC4112873 | BioStudies
2014-01-01 | S-EPMC4227214 | BioStudies
2019-01-01 | S-EPMC6625119 | BioStudies
1000-01-01 | S-EPMC6321508 | BioStudies