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Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression

Chinese Medical Journal 2011年第1期124卷 26-31页

作者： TIAN Xin-rui TIAN Xin-li BO Jian-ping LI Shao-gang LIU Zhuo-la NIU Bo Department of Respiratory Diseases Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China Capital Institute of Pediatrics Beijing 100020 China

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.

关键词： signal transducer and activator of transcription 6 antisense asthma lymphocyte Th2 cytokine

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Apoptosis induced by short hairpin RNA-mediated STAT6 gene silencing in human colon cancer cells

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Chinese Medical Journal 2006年第10期119卷 801-808页

作者： ZHANG Ming-sheng ZHOU Yun-feng ZHANG Wen-jie ZHANG Xiao-lian PAN Qin JI Xue-mei LUO Zhi-guo WU Jian-ping Department of Cancer Radio-Chemotherapy Zhongnan HospitalWuhan University Wuhan 430071 China Department of Surgery Pennsylvania State University College ofMedicine Hershey PA 17033 USA Department of Immunology Medical College of Wuhan UniversityWuhan 430071 China

Background The relationship between signal transduction and tumors has become one of the loci in cancer research. signal transducer and activator of the transcription 6 （STAT6） signaling pathway is found to be activated in some cancer cells. But the function of the pathway in cancer cells is unknown. This study was undertaken to investigate the effect of the Stat6 signaling pathway on apoptosis in human colon cancer cells （HT-29 cells） and the possible mechanism of Stat6 by RNA interference techniques.

关键词： RNA interference short hairpin RNA signal transducer and activator of transcription 6 tumor apoptosis

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