Distinct Responses to IL4 in Macrophages Mediated by JNK

IL(Interleukin)-4 is the main macrophage M2-type activator and induces an anti-inflammatory phenotype called alternative activation. The IL-4 signaling pathway involves the activation of STAT (Signal Transducer and Activator of Transcription)-6 and members of the MAPK (Mitogen-activated protein kina...

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Autores: Arpa Toribio, Luis, Batlle, Carlos, Jiang, Peijin, Caelles Franch, Carme, Lloberas Cavero, Jorge, Celada Cotarelo, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/201835
Acceso en línea:https://hdl.handle.net/2445/201835
Access Level:acceso abierto
Palabra clave:Macròfags
Inflamació
Macrophages
Inflammation
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spelling Distinct Responses to IL4 in Macrophages Mediated by JNKArpa Toribio, LuisBatlle, CarlosJiang, PeijinCaelles Franch, CarmeLloberas Cavero, JorgeCelada Cotarelo, AntonioMacròfagsInflamacióMacrophagesInflammationIL(Interleukin)-4 is the main macrophage M2-type activator and induces an anti-inflammatory phenotype called alternative activation. The IL-4 signaling pathway involves the activation of STAT (Signal Transducer and Activator of Transcription)-6 and members of the MAPK (Mitogen-activated protein kinase) family. In primary-bone-marrow-derived macrophages, we observed a strong activation of JNK (Jun N-terminal kinase)-1 at early time points of IL-4 stimulation. Using selective inhibitors and a knockout model, we explored the contribution of JNK-1 activation to macrophages' response to IL-4. Our findings indicate that JNK-1 regulates the IL-4-mediated expression of genes typically involved in alternative activation, such as Arginase 1 or Mannose receptor, but not others, such as SOCS (suppressor of cytokine signaling) 1 or p21Waf−1 (cyclin dependent kinase inhibitor 1A). Interestingly, we have observed that after macrophages are stimulated with IL-4, JNK-1 has the capacity to phosphorylate STAT-6 on serine but not on tyrosine. Chromatin immunoprecipitation assays revealed that functional JNK-1 is required for the recruitment of co-activators such as CBP (CREB-binding protein)/p300 on the promoter of Arginase 1 but not on p21Waf−1. Taken together, these data demonstrate the critical role of STAT-6 serine phosphorylation by JNK-1 in distinct macrophage responses to IL-4.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201835Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/cells12081127Cells, 2023, vol. 12, num. 8, p. 1127-1144https://doi.org/10.3390/cells12081127cc-by (c) Arpa Toribio, Luis et al., 2023https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2018352026-05-27T06:46:51Z
dc.title.none.fl_str_mv Distinct Responses to IL4 in Macrophages Mediated by JNK
title Distinct Responses to IL4 in Macrophages Mediated by JNK
spellingShingle Distinct Responses to IL4 in Macrophages Mediated by JNK
Arpa Toribio, Luis
Macròfags
Inflamació
Macrophages
Inflammation
title_short Distinct Responses to IL4 in Macrophages Mediated by JNK
title_full Distinct Responses to IL4 in Macrophages Mediated by JNK
title_fullStr Distinct Responses to IL4 in Macrophages Mediated by JNK
title_full_unstemmed Distinct Responses to IL4 in Macrophages Mediated by JNK
title_sort Distinct Responses to IL4 in Macrophages Mediated by JNK
dc.creator.none.fl_str_mv Arpa Toribio, Luis
Batlle, Carlos
Jiang, Peijin
Caelles Franch, Carme
Lloberas Cavero, Jorge
Celada Cotarelo, Antonio
author Arpa Toribio, Luis
author_facet Arpa Toribio, Luis
Batlle, Carlos
Jiang, Peijin
Caelles Franch, Carme
Lloberas Cavero, Jorge
Celada Cotarelo, Antonio
author_role author
author2 Batlle, Carlos
Jiang, Peijin
Caelles Franch, Carme
Lloberas Cavero, Jorge
Celada Cotarelo, Antonio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Macròfags
Inflamació
Macrophages
Inflammation
topic Macròfags
Inflamació
Macrophages
Inflammation
description IL(Interleukin)-4 is the main macrophage M2-type activator and induces an anti-inflammatory phenotype called alternative activation. The IL-4 signaling pathway involves the activation of STAT (Signal Transducer and Activator of Transcription)-6 and members of the MAPK (Mitogen-activated protein kinase) family. In primary-bone-marrow-derived macrophages, we observed a strong activation of JNK (Jun N-terminal kinase)-1 at early time points of IL-4 stimulation. Using selective inhibitors and a knockout model, we explored the contribution of JNK-1 activation to macrophages' response to IL-4. Our findings indicate that JNK-1 regulates the IL-4-mediated expression of genes typically involved in alternative activation, such as Arginase 1 or Mannose receptor, but not others, such as SOCS (suppressor of cytokine signaling) 1 or p21Waf−1 (cyclin dependent kinase inhibitor 1A). Interestingly, we have observed that after macrophages are stimulated with IL-4, JNK-1 has the capacity to phosphorylate STAT-6 on serine but not on tyrosine. Chromatin immunoprecipitation assays revealed that functional JNK-1 is required for the recruitment of co-activators such as CBP (CREB-binding protein)/p300 on the promoter of Arginase 1 but not on p21Waf−1. Taken together, these data demonstrate the critical role of STAT-6 serine phosphorylation by JNK-1 in distinct macrophage responses to IL-4.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/201835
url https://hdl.handle.net/2445/201835
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cells12081127
Cells, 2023, vol. 12, num. 8, p. 1127-1144
https://doi.org/10.3390/cells12081127
dc.rights.none.fl_str_mv cc-by (c) Arpa Toribio, Luis et al., 2023
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Arpa Toribio, Luis et al., 2023
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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