Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha

Autores
Landoni, Verónica Inés; de Campos Nebel, Ildefonso Marcelo; Schierloh, Luis Pablo; Calatayud, Cecilia Alicia; Fernández, Gabriela Cristina; Ramos, Maria Victoria; Rearte, María Bárbara; Palermo, Marina Sandra; Isturiz, Martín Amadeo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Calatayud, Cecilia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Fernández, Gabriela Cristina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Materia
Astrocytes
Shiga Toxin 1
Hemolytic-Uremic Syndrome
Brain Inflammation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/55332
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55332
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alphaLandoni, Verónica Inésde Campos Nebel, Ildefonso MarceloSchierloh, Luis PabloCalatayud, Cecilia AliciaFernández, Gabriela CristinaRamos, Maria VictoriaRearte, María BárbaraPalermo, Marina SandraIsturiz, Martín AmadeoAstrocytesShiga Toxin 1Hemolytic-Uremic SyndromeBrain Inflammationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury. Copyright © 2010, American Society for Microbiology. All Rights Reserved.Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Calatayud, Cecilia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Fernández, Gabriela Cristina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaAmerican Society for Microbiology2010-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55332Landoni, Verónica Inés; de Campos Nebel, Ildefonso Marcelo; Schierloh, Luis Pablo; Calatayud, Cecilia Alicia; Fernández, Gabriela Cristina; et al.; Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha; American Society for Microbiology; Infection and Immunity; 78; 3; 3-2010; 1193-12010019-9567CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00932-09info:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/78/3/1193info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:59Zoai:ri.conicet.gov.ar:11336/55332instacron: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:34982025-09-29 09:40:59.795CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
title Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
spellingShingle Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
Landoni, Verónica Inés
Astrocytes
Shiga Toxin 1
Hemolytic-Uremic Syndrome
Brain Inflammation
title_short Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
title_full Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
title_fullStr Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
title_full_unstemmed Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
title_sort Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha
dc.creator.none.fl_str_mv Landoni, Verónica Inés
de Campos Nebel, Ildefonso Marcelo
Schierloh, Luis Pablo
Calatayud, Cecilia Alicia
Fernández, Gabriela Cristina
Ramos, Maria Victoria
Rearte, María Bárbara
Palermo, Marina Sandra
Isturiz, Martín Amadeo
author Landoni, Verónica Inés
author_facet Landoni, Verónica Inés
de Campos Nebel, Ildefonso Marcelo
Schierloh, Luis Pablo
Calatayud, Cecilia Alicia
Fernández, Gabriela Cristina
Ramos, Maria Victoria
Rearte, María Bárbara
Palermo, Marina Sandra
Isturiz, Martín Amadeo
author_role author
author2 de Campos Nebel, Ildefonso Marcelo
Schierloh, Luis Pablo
Calatayud, Cecilia Alicia
Fernández, Gabriela Cristina
Ramos, Maria Victoria
Rearte, María Bárbara
Palermo, Marina Sandra
Isturiz, Martín Amadeo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Astrocytes
Shiga Toxin 1
Hemolytic-Uremic Syndrome
Brain Inflammation
topic Astrocytes
Shiga Toxin 1
Hemolytic-Uremic Syndrome
Brain Inflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Calatayud, Cecilia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; Argentina
Fil: Fernández, Gabriela Cristina. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Palermo, Marina Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
description Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
publishDate 2010
dc.date.none.fl_str_mv 2010-03
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/11336/55332
Landoni, Verónica Inés; de Campos Nebel, Ildefonso Marcelo; Schierloh, Luis Pablo; Calatayud, Cecilia Alicia; Fernández, Gabriela Cristina; et al.; Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha; American Society for Microbiology; Infection and Immunity; 78; 3; 3-2010; 1193-1201
0019-9567
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55332
identifier_str_mv Landoni, Verónica Inés; de Campos Nebel, Ildefonso Marcelo; Schierloh, Luis Pablo; Calatayud, Cecilia Alicia; Fernández, Gabriela Cristina; et al.; Shiga toxin 1-induced inflammatory response in lipopolysaccharide- sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha; American Society for Microbiology; Infection and Immunity; 78; 3; 3-2010; 1193-1201
0019-9567
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/78/3/1193
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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