dc.contributor.author | Teo, I. | |
dc.contributor.author | Toms, S.M. | |
dc.contributor.author | Marteyn, B. | |
dc.contributor.author | Barata, T.S. | |
dc.contributor.author | Simpson, P. | |
dc.contributor.author | Johnston, K.A. | |
dc.contributor.author | Schnupf, P. | |
dc.contributor.author | Puhar, A. | |
dc.contributor.author | Bell, T. | |
dc.contributor.author | Tang, C. | |
dc.contributor.author | Zloh, Mire | |
dc.contributor.author | Matthews, S. | |
dc.contributor.author | Rendle, P.M. | |
dc.contributor.author | Sansonetti, P.J. | |
dc.contributor.author | Shaunak, S. | |
dc.date.accessioned | 2013-03-14T11:19:47Z | |
dc.date.available | 2013-03-14T11:19:47Z | |
dc.date.issued | 2012-09-01 | |
dc.identifier.citation | Teo , I , Toms , S M , Marteyn , B , Barata , T S , Simpson , P , Johnston , K A , Schnupf , P , Puhar , A , Bell , T , Tang , C , Zloh , M , Matthews , S , Rendle , P M , Sansonetti , P J & Shaunak , S 2012 , ' Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers ' , EMBO Molecular Medicine , vol. 4 , no. 9 , pp. 866-881 . https://doi.org/10.1002/emmm.201201290 | |
dc.identifier.issn | 1757-4676 | |
dc.identifier.uri | http://hdl.handle.net/2299/10149 | |
dc.description | Copyright 2012 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 3.0), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes | |
dc.description.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 13.6kDa 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 3.3kDa 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 β-defensin, IL-10, interferon-β, transforming growth factor-β, 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. | en |
dc.format.extent | 16 | |
dc.format.extent | 1793055 | |
dc.language.iso | eng | |
dc.relation.ispartof | EMBO Molecular Medicine | |
dc.title | Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Health & Human Sciences Research Institute | |
dc.contributor.institution | Department of Pharmacy | |
dc.contributor.institution | Medicinal and Analytical Chemistry | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1002/emmm.201201290 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |