The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/58045 |
Resumo: | Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. |
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The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced ColitisInterleukin-10MacrophagesInflammationColitisTherapyCiências Médicas::Medicina BásicaScience & TechnologyInflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to AC (SFRH/BD/84704/2012). This article is a result of the project Norte-01-0145-FEDER-000012—Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). The MS lab is also financed by a FCT-ANR grant (FCTANR/BIM-MEC/0007/2013). This work was also backed by the COST Action BM1404 European Network of Investigators Triggering Exploratory Research on Myeloid Regulatory Cells (http://www.mye-euniter.eu), which is supported by the Horizon 2020—EU Framework Program Research and Innovation Programme. MS is a FCT Associate Investigator. AGC lab: This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER); by the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through FEDER; and by FEDER, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. PV is funded by ANR, through the project MYELOTEN (ANR-13-ISV1-0003-01)info:eu-repo/semantics/publishedVersionFrontiers MediaUniversidade do MinhoCardoso, AnaCastro, António G.Martins, Ana CatarinaCarriche, Guilhermina M.Murigneux, ValentineCastro, IsabelCumano, AnaVieira, PauloSaraiva, Margarida20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58045engCardoso, A., Gil Castro, A., Martins, A. C., et. al.(2018). The Dynamics of interleukin-10-afforded Protection during Dextran sulfate sodium-induced colitis. Frontiers in immunology, 9, 4001664-32241664-322410.3389/fimmu.2018.00400https://www.frontiersin.org/articles/10.3389/fimmu.2018.00400/fullinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:08:19Zoai:repositorium.sdum.uminho.pt:1822/58045Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:59:33.105936Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
title |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
spellingShingle |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis Cardoso, Ana Interleukin-10 Macrophages Inflammation Colitis Therapy Ciências Médicas::Medicina Básica Science & Technology |
title_short |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
title_full |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
title_fullStr |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
title_full_unstemmed |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
title_sort |
The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis |
author |
Cardoso, Ana |
author_facet |
Cardoso, Ana Castro, António G. Martins, Ana Catarina Carriche, Guilhermina M. Murigneux, Valentine Castro, Isabel Cumano, Ana Vieira, Paulo Saraiva, Margarida |
author_role |
author |
author2 |
Castro, António G. Martins, Ana Catarina Carriche, Guilhermina M. Murigneux, Valentine Castro, Isabel Cumano, Ana Vieira, Paulo Saraiva, Margarida |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Cardoso, Ana Castro, António G. Martins, Ana Catarina Carriche, Guilhermina M. Murigneux, Valentine Castro, Isabel Cumano, Ana Vieira, Paulo Saraiva, Margarida |
dc.subject.por.fl_str_mv |
Interleukin-10 Macrophages Inflammation Colitis Therapy Ciências Médicas::Medicina Básica Science & Technology |
topic |
Interleukin-10 Macrophages Inflammation Colitis Therapy Ciências Médicas::Medicina Básica Science & Technology |
description |
Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 2018-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/58045 |
url |
http://hdl.handle.net/1822/58045 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cardoso, A., Gil Castro, A., Martins, A. C., et. al.(2018). The Dynamics of interleukin-10-afforded Protection during Dextran sulfate sodium-induced colitis. Frontiers in immunology, 9, 400 1664-3224 1664-3224 10.3389/fimmu.2018.00400 https://www.frontiersin.org/articles/10.3389/fimmu.2018.00400/full |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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