Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin

Autores
Alvarez, Romina Soledad; Jancic, Carolina Cristina; Garimano, Nicolás Ezequiel; Sacerdoti, Flavia; Paton, Adrienne W.; Paton, James C.; Ibarra, Cristina Adriana; Amaral, María Marta
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells.
Fil: Alvarez, Romina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Garimano, Nicolás Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Paton, Adrienne W.. University of Adelaide; Australia
Fil: Paton, James C.. University of Adelaide; Australia
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Materia
CO-CULTURES
CYTOKINES
ENDOTHELIAL/EPITHELIAL HUMAN RENAL CELLS
HEMOLYTIC UREMIC SYNDROME
SHIGA TOXIN
SUBTILASE CYTOTOXIN
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:11336/120572

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxinAlvarez, Romina SoledadJancic, Carolina CristinaGarimano, Nicolás EzequielSacerdoti, FlaviaPaton, Adrienne W.Paton, James C.Ibarra, Cristina AdrianaAmaral, María MartaCO-CULTURESCYTOKINESENDOTHELIAL/EPITHELIAL HUMAN RENAL CELLSHEMOLYTIC UREMIC SYNDROMESHIGA TOXINSUBTILASE CYTOTOXINhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells.Fil: Alvarez, Romina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Garimano, Nicolás Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Paton, Adrienne W.. University of Adelaide; AustraliaFil: Paton, James C.. University of Adelaide; AustraliaFil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaMDPI AG2019-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120572Alvarez, Romina Soledad; Jancic, Carolina Cristina; Garimano, Nicolás Ezequiel; Sacerdoti, Flavia; Paton, Adrienne W.; et al.; Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin; MDPI AG; Toxins; 11; 11; 11-2019; 1-172072-6651CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/11/11/648info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891416/info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins11110648info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:21Zoai:ri.conicet.gov.ar:11336/120572instacron: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 09:54:22.238CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
title Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
spellingShingle Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
Alvarez, Romina Soledad
CO-CULTURES
CYTOKINES
ENDOTHELIAL/EPITHELIAL HUMAN RENAL CELLS
HEMOLYTIC UREMIC SYNDROME
SHIGA TOXIN
SUBTILASE CYTOTOXIN
title_short Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
title_full Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
title_fullStr Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
title_full_unstemmed Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
title_sort Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin
dc.creator.none.fl_str_mv Alvarez, Romina Soledad
Jancic, Carolina Cristina
Garimano, Nicolás Ezequiel
Sacerdoti, Flavia
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina Adriana
Amaral, María Marta
author Alvarez, Romina Soledad
author_facet Alvarez, Romina Soledad
Jancic, Carolina Cristina
Garimano, Nicolás Ezequiel
Sacerdoti, Flavia
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina Adriana
Amaral, María Marta
author_role author
author2 Jancic, Carolina Cristina
Garimano, Nicolás Ezequiel
Sacerdoti, Flavia
Paton, Adrienne W.
Paton, James C.
Ibarra, Cristina Adriana
Amaral, María Marta
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CO-CULTURES
CYTOKINES
ENDOTHELIAL/EPITHELIAL HUMAN RENAL CELLS
HEMOLYTIC UREMIC SYNDROME
SHIGA TOXIN
SUBTILASE CYTOTOXIN
topic CO-CULTURES
CYTOKINES
ENDOTHELIAL/EPITHELIAL HUMAN RENAL CELLS
HEMOLYTIC UREMIC SYNDROME
SHIGA TOXIN
SUBTILASE CYTOTOXIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells.
Fil: Alvarez, Romina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Garimano, Nicolás Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Sacerdoti, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Paton, Adrienne W.. University of Adelaide; Australia
Fil: Paton, James C.. University of Adelaide; Australia
Fil: Ibarra, Cristina Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Amaral, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
description Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichia coli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilase cytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2 and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. In this work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared to monocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 and TNF-α secretion was different between monocultures and co-cultures. After toxin treatments, high concentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast, low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion by HK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2 monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes, for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renal endothelial and epithelial cells.
publishDate 2019
dc.date.none.fl_str_mv 2019-11
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/11336/120572
Alvarez, Romina Soledad; Jancic, Carolina Cristina; Garimano, Nicolás Ezequiel; Sacerdoti, Flavia; Paton, Adrienne W.; et al.; Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin; MDPI AG; Toxins; 11; 11; 11-2019; 1-17
2072-6651
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120572
identifier_str_mv Alvarez, Romina Soledad; Jancic, Carolina Cristina; Garimano, Nicolás Ezequiel; Sacerdoti, Flavia; Paton, Adrienne W.; et al.; Crosstalk between human microvascular endothelial cells and tubular epithelial cells modulates pro-inflammatory responses induced by Shiga toxin type 2 and subtilase cytotoxin; MDPI AG; Toxins; 11; 11; 11-2019; 1-17
2072-6651
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891416/
info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins11110648
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
application/pdf
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dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
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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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