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Preventing acute gu...
Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers
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Teo, Ian (author)
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Toms, Steve M. (author)
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Marteyn, Benoit (author)
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Barata, Teresa S. (author)
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Simpson, Peter (author)
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Johnston, Karen A. (author)
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Schnupf, Pamela (author)
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- Puhar, Andrea, 1978- (author)
- Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire & Unité INSERM 786, Paris, France
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Bell, Tracey (author)
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Tang, Chris (author)
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Zloh, Mire (author)
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Matthews, Steve (author)
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Rendle, Phillip M. (author)
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Sansonetti, Philippe J. (author)
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Shaunak, Sunil (author)
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(creator_code:org_t)
- 2012-08-06
- 2012
- English.
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 4:9, s. 866-881
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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Teo, Ian
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Toms, Steve M.
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Marteyn, Benoit
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Barata, Teresa S ...
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Simpson, Peter
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Johnston, Karen ...
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show more...
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Schnupf, Pamela
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Puhar, Andrea, 1 ...
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Bell, Tracey
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Tang, Chris
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Zloh, Mire
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Matthews, Steve
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Rendle, Phillip ...
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Sansonetti, Phil ...
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Shaunak, Sunil
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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EMBO Molecular M ...
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Umeå University