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Vagus nerve controls resolution and pro-resolving mediators of inflammation
Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042652/ https://www.ncbi.nlm.nih.gov/pubmed/24863066 http://dx.doi.org/10.1084/jem.20132103 |
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author | Mirakaj, Valbona Dalli, Jesmond Granja, Tiago Rosenberger, Peter Serhan, Charles N. |
author_facet | Mirakaj, Valbona Dalli, Jesmond Granja, Tiago Rosenberger, Peter Serhan, Charles N. |
author_sort | Mirakaj, Valbona |
collection | PubMed |
description | Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1(+/−) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+). Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution. |
format | Online Article Text |
id | pubmed-4042652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40426522014-12-02 Vagus nerve controls resolution and pro-resolving mediators of inflammation Mirakaj, Valbona Dalli, Jesmond Granja, Tiago Rosenberger, Peter Serhan, Charles N. J Exp Med Article Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1(+/−) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+). Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution. The Rockefeller University Press 2014-06-02 /pmc/articles/PMC4042652/ /pubmed/24863066 http://dx.doi.org/10.1084/jem.20132103 Text en © 2014 Mirakaj et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Mirakaj, Valbona Dalli, Jesmond Granja, Tiago Rosenberger, Peter Serhan, Charles N. Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title | Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title_full | Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title_fullStr | Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title_full_unstemmed | Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title_short | Vagus nerve controls resolution and pro-resolving mediators of inflammation |
title_sort | vagus nerve controls resolution and pro-resolving mediators of inflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042652/ https://www.ncbi.nlm.nih.gov/pubmed/24863066 http://dx.doi.org/10.1084/jem.20132103 |
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