Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.

Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering o...

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Main Authors: Ma Paz Zafra, Carla Mazzeo, Cristina Gámez, Ainara Rodriguez Marco, Ana de Zulueta, Veronica Sanz, Izaskun Bilbao, Jesús Ruiz-Cabello, Jose M Zubeldia, Victoria del Pozo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3956882?pdf=render
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author Ma Paz Zafra
Carla Mazzeo
Cristina Gámez
Ainara Rodriguez Marco
Ana de Zulueta
Veronica Sanz
Izaskun Bilbao
Jesús Ruiz-Cabello
Jose M Zubeldia
Victoria del Pozo
author_facet Ma Paz Zafra
Carla Mazzeo
Cristina Gámez
Ainara Rodriguez Marco
Ana de Zulueta
Veronica Sanz
Izaskun Bilbao
Jesús Ruiz-Cabello
Jose M Zubeldia
Victoria del Pozo
author_sort Ma Paz Zafra
collection DOAJ
description Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.
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spelling doaj.art-513f06e7d0614026964c286965f5ff132022-12-22T01:18:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9199610.1371/journal.pone.0091996Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.Ma Paz ZafraCarla MazzeoCristina GámezAinara Rodriguez MarcoAna de ZuluetaVeronica SanzIzaskun BilbaoJesús Ruiz-CabelloJose M ZubeldiaVictoria del PozoSuppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.http://europepmc.org/articles/PMC3956882?pdf=render
spellingShingle Ma Paz Zafra
Carla Mazzeo
Cristina Gámez
Ainara Rodriguez Marco
Ana de Zulueta
Veronica Sanz
Izaskun Bilbao
Jesús Ruiz-Cabello
Jose M Zubeldia
Victoria del Pozo
Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
PLoS ONE
title Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
title_full Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
title_fullStr Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
title_full_unstemmed Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
title_short Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.
title_sort gene silencing of socs3 by sirna intranasal delivery inhibits asthma phenotype in mice
url http://europepmc.org/articles/PMC3956882?pdf=render
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