Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis

Autores
Kolb, Martin; Margetts, Peter J.; Anthony, Daniel C.; Pitossi, Fernando Juan; Gauldie, Jack
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.
Fil: Kolb, Martin. McMaster University; Canadá
Fil: Margetts, Peter J.. McMaster University; Canadá
Fil: Anthony, Daniel C.. University of Southampton; Reino Unido
Fil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Gauldie, Jack. McMaster University; Canadá
Materia
TGF-â
IL-1
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:11336/47741
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosisKolb, MartinMargetts, Peter J.Anthony, Daniel C.Pitossi, Fernando JuanGauldie, JackTGF-âIL-1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.Fil: Kolb, Martin. McMaster University; CanadáFil: Margetts, Peter J.. McMaster University; CanadáFil: Anthony, Daniel C.. University of Southampton; Reino UnidoFil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gauldie, Jack. McMaster University; CanadáAmerican Society for Clinical Investigation2001-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47741Kolb, Martin; Margetts, Peter J.; Anthony, Daniel C.; Pitossi, Fernando Juan; Gauldie, Jack; Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 107; 12; 6-2001; 1529-15360021-97381558-8238CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/12568info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI12568info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:50Zoai:ri.conicet.gov.ar:11336/47741instacron: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 09:45:50.67CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
title Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
spellingShingle Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
Kolb, Martin
TGF-â
IL-1
title_short Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
title_full Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
title_fullStr Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
title_full_unstemmed Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
title_sort Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis
dc.creator.none.fl_str_mv Kolb, Martin
Margetts, Peter J.
Anthony, Daniel C.
Pitossi, Fernando Juan
Gauldie, Jack
author Kolb, Martin
author_facet Kolb, Martin
Margetts, Peter J.
Anthony, Daniel C.
Pitossi, Fernando Juan
Gauldie, Jack
author_role author
author2 Margetts, Peter J.
Anthony, Daniel C.
Pitossi, Fernando Juan
Gauldie, Jack
author2_role author
author
author
author
dc.subject.none.fl_str_mv TGF-â
IL-1
topic TGF-â
IL-1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.
Fil: Kolb, Martin. McMaster University; Canadá
Fil: Margetts, Peter J.. McMaster University; Canadá
Fil: Anthony, Daniel C.. University of Southampton; Reino Unido
Fil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Gauldie, Jack. McMaster University; Canadá
description IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.
publishDate 2001
dc.date.none.fl_str_mv 2001-06
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/11336/47741
Kolb, Martin; Margetts, Peter J.; Anthony, Daniel C.; Pitossi, Fernando Juan; Gauldie, Jack; Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 107; 12; 6-2001; 1529-1536
0021-9738
1558-8238
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47741
identifier_str_mv Kolb, Martin; Margetts, Peter J.; Anthony, Daniel C.; Pitossi, Fernando Juan; Gauldie, Jack; Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis; American Society for Clinical Investigation; Journal of Clinical Investigation; 107; 12; 6-2001; 1529-1536
0021-9738
1558-8238
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.jci.org/articles/view/12568
info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI12568
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
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
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
_version_ 1842268757404155904
score 13.13397

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