Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression
Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression作者机构：Department of Respiratory Diseases Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China Capital Institute of Pediatrics Beijing 100020 China
出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)
年 卷 期：2011年第124卷第1期
页 面：26-31页
核心收录：
主 题：signal transducer and activator of transcription 6 antisense asthma lymphocyte Th2 cytokine
摘 要：Background The signal transducer and activator of transcription 6 （STAT6） expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 （Th2） cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation. Methods In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide （ASODN） overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA （pANTI-STAT6）, then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma. Results In vitro, we showed suppression of STAT6 expression and interleukin （IL）-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin （OVA）-sensitized mice, local intranasal administration of fluorescein isothiocyanate （FITC）-Iabeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production. Conclusion These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.
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