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Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma
Guidance cues such as semaphorins are attractive novel therapeutic targets for allergic disorders. We have previously described an inhibitory effect of semaphorin 3E (Sema3E) on human airway smooth muscle cell function. We have further addressed a canonical role for Sema3E in acute model of allergic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716780/ https://www.ncbi.nlm.nih.gov/pubmed/29228740 http://dx.doi.org/10.18632/oncotarget.22144 |
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author | Movassagh, Hesam Shan, Lianyu Duke-Cohan, Jonathan S. Chakir, Jamila Halayko, Andrew J. Koussih, Latifa Gounni, Abdelilah S. |
author_facet | Movassagh, Hesam Shan, Lianyu Duke-Cohan, Jonathan S. Chakir, Jamila Halayko, Andrew J. Koussih, Latifa Gounni, Abdelilah S. |
author_sort | Movassagh, Hesam |
collection | PubMed |
description | Guidance cues such as semaphorins are attractive novel therapeutic targets for allergic disorders. We have previously described an inhibitory effect of semaphorin 3E (Sema3E) on human airway smooth muscle cell function. We have further addressed a canonical role for Sema3E in acute model of allergic asthma in vivo. Considering the chronic nature of the disease, the potential implication of Sema3E to alleviate long-lasting deficits should be investigated. Expression of Sema3E in a chronic model of allergic asthma was assessed after exposure to house dust mite (HDM) as a clinically relevant allergen. Chronic features of allergic asthma including airway hyper-responsiveness (AHR), inflammation, and remodeling were studied in Sema3E-deficient mice. Additionally, the effect of exogenous Sema3E treatment was evaluated in prophylactic and therapeutic experimental models. We have demonstrated that expression of Sema3E is robustly suppressed in the airways upon chronic HDM exposure. Chronic allergic airway disease was significantly augmented in Sema3E-deficient mouse model which was associated with an increased AHR, remodeling, and Th2/Th17 inflammation. Intranasal Sema3E administration restored chronic deficits of allergic asthma in mice. Data from this study unveil a key regulatory role of Sema3E in chronic course of asthma via orchestration of impaired inflammatory and remodeling responses. |
format | Online Article Text |
id | pubmed-5716780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57167802017-12-08 Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma Movassagh, Hesam Shan, Lianyu Duke-Cohan, Jonathan S. Chakir, Jamila Halayko, Andrew J. Koussih, Latifa Gounni, Abdelilah S. Oncotarget Research Paper Guidance cues such as semaphorins are attractive novel therapeutic targets for allergic disorders. We have previously described an inhibitory effect of semaphorin 3E (Sema3E) on human airway smooth muscle cell function. We have further addressed a canonical role for Sema3E in acute model of allergic asthma in vivo. Considering the chronic nature of the disease, the potential implication of Sema3E to alleviate long-lasting deficits should be investigated. Expression of Sema3E in a chronic model of allergic asthma was assessed after exposure to house dust mite (HDM) as a clinically relevant allergen. Chronic features of allergic asthma including airway hyper-responsiveness (AHR), inflammation, and remodeling were studied in Sema3E-deficient mice. Additionally, the effect of exogenous Sema3E treatment was evaluated in prophylactic and therapeutic experimental models. We have demonstrated that expression of Sema3E is robustly suppressed in the airways upon chronic HDM exposure. Chronic allergic airway disease was significantly augmented in Sema3E-deficient mouse model which was associated with an increased AHR, remodeling, and Th2/Th17 inflammation. Intranasal Sema3E administration restored chronic deficits of allergic asthma in mice. Data from this study unveil a key regulatory role of Sema3E in chronic course of asthma via orchestration of impaired inflammatory and remodeling responses. Impact Journals LLC 2017-10-27 /pmc/articles/PMC5716780/ /pubmed/29228740 http://dx.doi.org/10.18632/oncotarget.22144 Text en Copyright: © 2017 Movassagh et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Movassagh, Hesam Shan, Lianyu Duke-Cohan, Jonathan S. Chakir, Jamila Halayko, Andrew J. Koussih, Latifa Gounni, Abdelilah S. Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title | Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title_full | Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title_fullStr | Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title_full_unstemmed | Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title_short | Downregulation of semaphorin 3E promotes hallmarks of experimental chronic allergic asthma |
title_sort | downregulation of semaphorin 3e promotes hallmarks of experimental chronic allergic asthma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716780/ https://www.ncbi.nlm.nih.gov/pubmed/29228740 http://dx.doi.org/10.18632/oncotarget.22144 |
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