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

Abstract

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.

• 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
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e91996 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24637581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• MicroRNAs
• RNA, Small Interfering
• Socs3 protein, mouse
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Collagen

Topics

• Animals
• Asthma (diagnosis, genetics, immunology, metabolism)
• Collagen (metabolism)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation
• Gene Knockdown Techniques
• Gene Silencing
• Gene Transfer Techniques
• Immunity, Humoral
• Lung (immunology, metabolism, pathology)
• Male
• Mice
• MicroRNAs (genetics)
• Phenotype
• RNA, Small Interfering (administration & dosage, genetics)
• Respiratory Mucosa (metabolism, pathology)
• Signal Transduction
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• X-Ray Microtomography