A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model

Autores
del Carmen, Silvina Andrea; Zurita Turk, Meritxell; Alvarenga Lima, Fernanda; Coelho Dos Santos, Janete; Leclercq, Sophie Yvette; Chatel, Jean-Marc; Azevedo, Vasco; de Moreno, Maria Alejandra; Miyoshi, Anderson; Leblanc, Jean Guy Joseph
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 anti-inflammatory 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.
Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Fil: Zurita Turk, Meritxell. Universidade Federal Do Minas Gerais; Brasil;
Fil: Alvarenga Lima, Fernanda. Universidade Federal Do Minas Gerais; Brasil;
Fil: Coelho Dos Santos, Janete. No especifíca;
Fil: Leclercq, Sophie Yvette. No especifíca;
Fil: Chatel, Jean-Marc. Institut National de la Recherche Agronomique; Francia;
Fil: Azevedo, Vasco. Universidade Federal Do Minas Gerais; Brasil;
Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Fil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais; Brasil;
Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento de Investigacion. Catedra de Metodologia de la Invest.cientifica; Argentina
Materia
CROHN'S DISEASE
DNA DELIVERY SYSTEM
INTERLEUKIN-10
LACTOCOCCUS LACTIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/2568

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse modeldel Carmen, Silvina AndreaZurita Turk, MeritxellAlvarenga Lima, FernandaCoelho Dos Santos, JaneteLeclercq, Sophie YvetteChatel, Jean-MarcAzevedo, Vascode Moreno, Maria AlejandraMiyoshi, AndersonLeblanc, Jean Guy JosephCROHN'S DISEASEDNA DELIVERY SYSTEMINTERLEUKIN-10LACTOCOCCUS LACTIShttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Inflammatory 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 anti-inflammatory 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.Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Zurita Turk, Meritxell. Universidade Federal Do Minas Gerais; Brasil;Fil: Alvarenga Lima, Fernanda. Universidade Federal Do Minas Gerais; Brasil;Fil: Coelho Dos Santos, Janete. No especifíca;Fil: Leclercq, Sophie Yvette. No especifíca;Fil: Chatel, Jean-Marc. Institut National de la Recherche Agronomique; Francia;Fil: Azevedo, Vasco. Universidade Federal Do Minas Gerais; Brasil;Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais; Brasil;Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento de Investigacion. Catedra de Metodologia de la Invest.cientifica; ArgentinaBiolife Sas2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2568del Carmen, Silvina Andrea; Zurita Turk, Meritxell; Alvarenga Lima, Fernanda; Coelho Dos Santos, Janete; Leclercq, Sophie Yvette; et al.; A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model; Biolife Sas; European Journal Of Inflammation; 11; 3; 9-2013; 641-6541721-727Xenginfo:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/abs/10.1177/1721727X1301100308info:eu-repo/semantics/altIdentifier/doi/10.1177/1721727X1301100308info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:50Zoai:ri.conicet.gov.ar:11336/2568instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:51.133CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model
title A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model
spellingShingle A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model
del Carmen, Silvina Andrea
CROHN'S DISEASE
DNA DELIVERY SYSTEM
INTERLEUKIN-10
LACTOCOCCUS LACTIS
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 A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model
dc.creator.none.fl_str_mv del Carmen, Silvina Andrea
Zurita Turk, Meritxell
Alvarenga Lima, Fernanda
Coelho Dos Santos, Janete
Leclercq, Sophie Yvette
Chatel, Jean-Marc
Azevedo, Vasco
de Moreno, Maria Alejandra
Miyoshi, Anderson
Leblanc, Jean Guy Joseph
author del Carmen, Silvina Andrea
author_facet del Carmen, Silvina Andrea
Zurita Turk, Meritxell
Alvarenga Lima, Fernanda
Coelho Dos Santos, Janete
Leclercq, Sophie Yvette
Chatel, Jean-Marc
Azevedo, Vasco
de Moreno, Maria Alejandra
Miyoshi, Anderson
Leblanc, Jean Guy Joseph
author_role author
author2 Zurita Turk, Meritxell
Alvarenga Lima, Fernanda
Coelho Dos Santos, Janete
Leclercq, Sophie Yvette
Chatel, Jean-Marc
Azevedo, Vasco
de Moreno, Maria Alejandra
Miyoshi, Anderson
Leblanc, Jean Guy Joseph
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CROHN'S DISEASE
DNA DELIVERY SYSTEM
INTERLEUKIN-10
LACTOCOCCUS LACTIS
topic CROHN'S DISEASE
DNA DELIVERY SYSTEM
INTERLEUKIN-10
LACTOCOCCUS LACTIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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 anti-inflammatory 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.
Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Fil: Zurita Turk, Meritxell. Universidade Federal Do Minas Gerais; Brasil;
Fil: Alvarenga Lima, Fernanda. Universidade Federal Do Minas Gerais; Brasil;
Fil: Coelho Dos Santos, Janete. No especifíca;
Fil: Leclercq, Sophie Yvette. No especifíca;
Fil: Chatel, Jean-Marc. Institut National de la Recherche Agronomique; Francia;
Fil: Azevedo, Vasco. Universidade Federal Do Minas Gerais; Brasil;
Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Fil: Miyoshi, Anderson. Universidade Federal Do Minas Gerais; Brasil;
Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina. Universidad Nacional de Tucuman. Facultad de Medicina. Departamento de Investigacion. Catedra de Metodologia de la Invest.cientifica; Argentina
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 anti-inflammatory 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/2568
del Carmen, Silvina Andrea; Zurita Turk, Meritxell; Alvarenga Lima, Fernanda; Coelho Dos Santos, Janete; Leclercq, Sophie Yvette; et al.; A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model; Biolife Sas; European Journal Of Inflammation; 11; 3; 9-2013; 641-654
1721-727X
url http://hdl.handle.net/11336/2568
identifier_str_mv del Carmen, Silvina Andrea; Zurita Turk, Meritxell; Alvarenga Lima, Fernanda; Coelho Dos Santos, Janete; Leclercq, Sophie Yvette; et al.; A novel interleukin-10 DNA mucosal delivery system attenuates intestinal inflammation in a mouse model; Biolife Sas; European Journal Of Inflammation; 11; 3; 9-2013; 641-654
1721-727X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/abs/10.1177/1721727X1301100308
info:eu-repo/semantics/altIdentifier/doi/10.1177/1721727X1301100308
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Biolife Sas
publisher.none.fl_str_mv Biolife Sas
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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