A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model
Inflammatory bowel diseases (IBD) describe a group of complex intestinal disorders characterized by inflammation in the gastrointestinal tract. Current treatments for IBD include the use of antiinflammatory drugs; furthermore, recombinant lactic acid bacteria have been used as a therapeutic vehicle...
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2013-09-01
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Series: | European Journal of Inflammation |
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doaj-2695c4d147e5478d92a27f5fc6b47c612020-11-25T02:54:19ZengSAGE PublishingEuropean Journal of Inflammation1721-727X2013-09-011110.1177/1721727X1301100308A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse ModelS. Del Carmen0M. Zurita-Turk1F. Alvarenga Lima2J.S. Coelho Dos Santos3S.Y. Leclercq4J.-M. Chatel5V. Azevedo6A. De Moreno De Leblanc7A. Miyoshi8J.G. Leblanc9 Centro de Referenciapara Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina (T4000ILC) Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, Brazil Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, Brazil Laboratório de Inovação Biotecnológica, Fundação Ezequiel Dias (FUNED), Belo Horizonte, Minas Gerais, Brasil Laboratório de Inovação Biotecnológica, Fundação Ezequiel Dias (FUNED), Belo Horizonte, Minas Gerais, Brasil INRA, UMR1319 Micalis, Commensal and Probiotics-Host Interactions Laboratory, Jouy-en-Josas Cedex, France Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, Brazil Centro de Referenciapara Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina (T4000ILC) Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB/UFMG), Belo Horizonte, Brazil Cátedra de Metodologia de la Investigación Cientifíca, Facultad de Medicina, Universidad Nacional de Tucumán, San Miguel de Tucumán, ArgentinaInflammatory bowel diseases (IBD) describe a group of complex intestinal disorders characterized by inflammation in the gastrointestinal tract. Current treatments for IBD include the use of antiinflammatory drugs; furthermore, recombinant lactic acid bacteria have been used as a therapeutic vehicle for anti-inflammatory agents in IBD models. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines; however, its oral administration is limited because it is quickly degraded in the gastrointestinal tract and systemic treatments have led to undesirable side effects. In this study, an engineered invasive strain of Lactococcus (L.) lactis producing Fibronectin Binding Protein A (FnBPA+), from Staphylococcus aureus capable of delivering, directly inside eukaryotic cells, an eukaryotic DNA expression vector containing the ORF coding for IL-10 of Mus musculus (pValac: il-10 ) was developed and its functionality was evaluated using in vitro and in vivo assays. Functionality of the plasmid and the invasive strain was demonstrated by transfection and invasiveness assays using cell cultures and in vivo in mice by fluorescence microscopy. TNBS inoculated mice that received this novel strain showed lower damage scores in their large intestines (at both macroscopic and microscopic levels), lower microbial translocation to liver, and increased anti-inflammatory/pro-inflammatory cytokine ratios compared to mice that received L. lactis FnBPA+ without the pValac: il-10 plasmid. The effectiveness was demonstrated of this novel DNA delivery therapeutic strategy in the prevention of inflammation using a murine model of colitis.https://doi.org/10.1177/1721727X1301100308 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
S. Del Carmen M. Zurita-Turk F. Alvarenga Lima J.S. Coelho Dos Santos S.Y. Leclercq J.-M. Chatel V. Azevedo A. De Moreno De Leblanc A. Miyoshi J.G. Leblanc |
spellingShingle |
S. Del Carmen M. Zurita-Turk F. Alvarenga Lima J.S. Coelho Dos Santos S.Y. Leclercq J.-M. Chatel V. Azevedo A. De Moreno De Leblanc A. Miyoshi J.G. Leblanc A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model European Journal of Inflammation |
author_facet |
S. Del Carmen M. Zurita-Turk F. Alvarenga Lima J.S. Coelho Dos Santos S.Y. Leclercq J.-M. Chatel V. Azevedo A. De Moreno De Leblanc A. Miyoshi J.G. Leblanc |
author_sort |
S. Del Carmen |
title |
A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model |
title_short |
A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model |
title_full |
A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model |
title_fullStr |
A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model |
title_full_unstemmed |
A Novel Interleukin-10 Dna Mucosal Delivery System Attenuates Intestinal Inflammation in a Mouse Model |
title_sort |
novel interleukin-10 dna mucosal delivery system attenuates intestinal inflammation in a mouse model |
publisher |
SAGE Publishing |
series |
European Journal of Inflammation |
issn |
1721-727X |
publishDate |
2013-09-01 |
description |
Inflammatory bowel diseases (IBD) describe a group of complex intestinal disorders characterized by inflammation in the gastrointestinal tract. Current treatments for IBD include the use of antiinflammatory drugs; furthermore, recombinant lactic acid bacteria have been used as a therapeutic vehicle for anti-inflammatory agents in IBD models. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines; however, its oral administration is limited because it is quickly degraded in the gastrointestinal tract and systemic treatments have led to undesirable side effects. In this study, an engineered invasive strain of Lactococcus (L.) lactis producing Fibronectin Binding Protein A (FnBPA+), from Staphylococcus aureus capable of delivering, directly inside eukaryotic cells, an eukaryotic DNA expression vector containing the ORF coding for IL-10 of Mus musculus (pValac: il-10 ) was developed and its functionality was evaluated using in vitro and in vivo assays. Functionality of the plasmid and the invasive strain was demonstrated by transfection and invasiveness assays using cell cultures and in vivo in mice by fluorescence microscopy. TNBS inoculated mice that received this novel strain showed lower damage scores in their large intestines (at both macroscopic and microscopic levels), lower microbial translocation to liver, and increased anti-inflammatory/pro-inflammatory cytokine ratios compared to mice that received L. lactis FnBPA+ without the pValac: il-10 plasmid. The effectiveness was demonstrated of this novel DNA delivery therapeutic strategy in the prevention of inflammation using a murine model of colitis. |
url |
https://doi.org/10.1177/1721727X1301100308 |
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