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Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage

Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavengi...

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Autores principales: Zhao, Xiurong, Ting, Shun-Ming, Liu, Chin-Hsuan, Sun, Guanghua, Kruzel, Marian, Roy-O’Reilly, Meaghan, Aronowski, Jaroslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605643/
https://www.ncbi.nlm.nih.gov/pubmed/28928459
http://dx.doi.org/10.1038/s41467-017-00770-7
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author Zhao, Xiurong
Ting, Shun-Ming
Liu, Chin-Hsuan
Sun, Guanghua
Kruzel, Marian
Roy-O’Reilly, Meaghan
Aronowski, Jaroslaw
author_facet Zhao, Xiurong
Ting, Shun-Ming
Liu, Chin-Hsuan
Sun, Guanghua
Kruzel, Marian
Roy-O’Reilly, Meaghan
Aronowski, Jaroslaw
author_sort Zhao, Xiurong
collection PubMed
description Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavenging lactoferrin that may limit hematoma/iron-mediated brain injury after intracerebral hemorrhage. Here, we show that the immunoregulatory cytokine interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage. Data from rodent models indicate that interleukin-27 modifies neutrophil maturation in the bone marrow, suppressing their production of pro-inflammatory/cytotoxic products while increasing their production of beneficial iron-scavenging molecules, including lactoferrin. Finally, interleukin-27 or lactoferrin administration results in reduced edema, enhanced hematoma clearance, and improved neurological outcomes in an animal model of intracerebral hemorrhage. These results suggest that interleukin-27/lactoferrin-mediated modulations of neutrophil function may represent a therapeutically viable concept for the modification of neutrophils toward a “beneficial” phenotype for the treatment of intracerebral hemorrhage.
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spelling pubmed-56056432017-09-22 Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage Zhao, Xiurong Ting, Shun-Ming Liu, Chin-Hsuan Sun, Guanghua Kruzel, Marian Roy-O’Reilly, Meaghan Aronowski, Jaroslaw Nat Commun Article Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavenging lactoferrin that may limit hematoma/iron-mediated brain injury after intracerebral hemorrhage. Here, we show that the immunoregulatory cytokine interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage. Data from rodent models indicate that interleukin-27 modifies neutrophil maturation in the bone marrow, suppressing their production of pro-inflammatory/cytotoxic products while increasing their production of beneficial iron-scavenging molecules, including lactoferrin. Finally, interleukin-27 or lactoferrin administration results in reduced edema, enhanced hematoma clearance, and improved neurological outcomes in an animal model of intracerebral hemorrhage. These results suggest that interleukin-27/lactoferrin-mediated modulations of neutrophil function may represent a therapeutically viable concept for the modification of neutrophils toward a “beneficial” phenotype for the treatment of intracerebral hemorrhage. Nature Publishing Group UK 2017-09-19 /pmc/articles/PMC5605643/ /pubmed/28928459 http://dx.doi.org/10.1038/s41467-017-00770-7 Text en © The Author(s) 2017 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
Zhao, Xiurong
Ting, Shun-Ming
Liu, Chin-Hsuan
Sun, Guanghua
Kruzel, Marian
Roy-O’Reilly, Meaghan
Aronowski, Jaroslaw
Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title_full Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title_fullStr Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title_full_unstemmed Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title_short Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage
title_sort neutrophil polarization by il-27 as a therapeutic target for intracerebral hemorrhage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605643/
https://www.ncbi.nlm.nih.gov/pubmed/28928459
http://dx.doi.org/10.1038/s41467-017-00770-7
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