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Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia
BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652356/ https://www.ncbi.nlm.nih.gov/pubmed/26581581 http://dx.doi.org/10.1186/s12974-015-0427-0 |
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author | Inácio, Ana R. Liu, Yawei Clausen, Bettina H. Svensson, Martina Kucharz, Krzysztof Yang, Yiyi Stankovich, Totte Khorooshi, Reza Lambertsen, Kate L. Issazadeh-Navikas, Shohreh Deierborg, Tomas |
author_facet | Inácio, Ana R. Liu, Yawei Clausen, Bettina H. Svensson, Martina Kucharz, Krzysztof Yang, Yiyi Stankovich, Totte Khorooshi, Reza Lambertsen, Kate L. Issazadeh-Navikas, Shohreh Deierborg, Tomas |
author_sort | Inácio, Ana R. |
collection | PubMed |
description | BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. METHODS: To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2–3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. CONCLUSIONS: We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0427-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4652356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46523562015-11-20 Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia Inácio, Ana R. Liu, Yawei Clausen, Bettina H. Svensson, Martina Kucharz, Krzysztof Yang, Yiyi Stankovich, Totte Khorooshi, Reza Lambertsen, Kate L. Issazadeh-Navikas, Shohreh Deierborg, Tomas J Neuroinflammation Research BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. METHODS: To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2–3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. CONCLUSIONS: We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0427-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-18 /pmc/articles/PMC4652356/ /pubmed/26581581 http://dx.doi.org/10.1186/s12974-015-0427-0 Text en © Inácio et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Inácio, Ana R. Liu, Yawei Clausen, Bettina H. Svensson, Martina Kucharz, Krzysztof Yang, Yiyi Stankovich, Totte Khorooshi, Reza Lambertsen, Kate L. Issazadeh-Navikas, Shohreh Deierborg, Tomas Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title | Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title_full | Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title_fullStr | Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title_full_unstemmed | Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title_short | Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
title_sort | endogenous ifn-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652356/ https://www.ncbi.nlm.nih.gov/pubmed/26581581 http://dx.doi.org/10.1186/s12974-015-0427-0 |
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