Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice

被引：42

作者：

Paz Zafra, Ma ^{[1
,2
]}

Mazzeo, Carla ^{[1
,2
]}

Gamez, Cristina ^{[1
,2
]}

Rodriguez Marco, Ainara ^{[1
]}

de Zulueta, Ana ^{[1
,2
]}

Sanz, Veronica ^{[1
,2
]}

Bilbao, Izaskun ^{[2
,3
,4
]}

Ruiz-Cabello, Jesus ^{[2
,3
,4
]}

Zubeldia, Jose M. ^{[5
,6
]}

del Pozo, Victoria ^{[1
,2
]}

机构：

[1] IIS Fdn Jimenez Diaz, Dept Immunol, Madrid, Spain

[2] CIBER Enfermedades Resp, Madrid, Spain

[3] Ctr Nacl Invest Cardiovasc, Adv Imaging Unit, Madrid, Spain

[4] Univ Complutense Madrid, Madrid, Spain

[5] Hosp Gen Gregorio Maranon, Allergy Sect, Madrid, Spain

[6] Hosp Gen Gregorio Maranon, Expt Med Unit, Madrid, Spain

来源：

PLOS ONE | 2014年 / 9卷 / 03期

关键词：

SMALL INTERFERING RNA; AIRWAY HYPERRESPONSIVENESS; IMMUNE-RESPONSES; INFLAMMATION; SUPPRESSOR; EXPRESSION; CELLS; THERAPY; RHOA;

D O I：

10.1371/journal.pone.0091996

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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