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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...

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Autores principales: Movassagh, Hesam, Shan, Lianyu, Duke-Cohan, Jonathan S., Chakir, Jamila, Halayko, Andrew J., Koussih, Latifa, Gounni, Abdelilah S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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