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Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation
Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macroph...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986789/ https://www.ncbi.nlm.nih.gov/pubmed/29867198 http://dx.doi.org/10.1038/s41419-018-0710-y |
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author | Marwick, John A. Mills, Ross Kay, Oliver Michail, Kyriakos Stephen, Jillian Rossi, Adriano G. Dransfield, Ian Hirani, Nikhil |
author_facet | Marwick, John A. Mills, Ross Kay, Oliver Michail, Kyriakos Stephen, Jillian Rossi, Adriano G. Dransfield, Ian Hirani, Nikhil |
author_sort | Marwick, John A. |
collection | PubMed |
description | Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macrophage NF-κB activation occurs through a blockade in transforming growth factor β-activated kinase 1 (TAK1) and IKKβ activation. As a consequence, NF-κB (p65) phosphorylation is reduced, its translocation to the nucleus is inhibited and NF-κB-mediated inflammatory cytokine transcription is suppressed. Gene Set Enrichment Analysis reveals that this suppression of NF-κB activation is not restricted to post-translational modifications of the canonical NF-κB pathway, but is also imprinted at the transcriptional level. Thus neutrophils exert a sustained anti-inflammatory phenotypic reprogramming of the macrophage, which is reflected by the sustained reduction in the release of pro- but not anti- inflammatory cytokines from the macrophage. Together, our findings identify a novel apoptosis-independent mechanism by which neutrophils regulate the mediator profile and reprogramming of monocytes/macrophages, representing an important nodal point for inflammatory control. |
format | Online Article Text |
id | pubmed-5986789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59867892018-06-05 Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation Marwick, John A. Mills, Ross Kay, Oliver Michail, Kyriakos Stephen, Jillian Rossi, Adriano G. Dransfield, Ian Hirani, Nikhil Cell Death Dis Article Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macrophage NF-κB activation occurs through a blockade in transforming growth factor β-activated kinase 1 (TAK1) and IKKβ activation. As a consequence, NF-κB (p65) phosphorylation is reduced, its translocation to the nucleus is inhibited and NF-κB-mediated inflammatory cytokine transcription is suppressed. Gene Set Enrichment Analysis reveals that this suppression of NF-κB activation is not restricted to post-translational modifications of the canonical NF-κB pathway, but is also imprinted at the transcriptional level. Thus neutrophils exert a sustained anti-inflammatory phenotypic reprogramming of the macrophage, which is reflected by the sustained reduction in the release of pro- but not anti- inflammatory cytokines from the macrophage. Together, our findings identify a novel apoptosis-independent mechanism by which neutrophils regulate the mediator profile and reprogramming of monocytes/macrophages, representing an important nodal point for inflammatory control. Nature Publishing Group UK 2018-06-04 /pmc/articles/PMC5986789/ /pubmed/29867198 http://dx.doi.org/10.1038/s41419-018-0710-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Marwick, John A. Mills, Ross Kay, Oliver Michail, Kyriakos Stephen, Jillian Rossi, Adriano G. Dransfield, Ian Hirani, Nikhil Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title | Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title_full | Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title_fullStr | Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title_full_unstemmed | Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title_short | Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation |
title_sort | neutrophils induce macrophage anti-inflammatory reprogramming by suppressing nf-κb activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986789/ https://www.ncbi.nlm.nih.gov/pubmed/29867198 http://dx.doi.org/10.1038/s41419-018-0710-y |
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