Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 26-31, 2011.
Article
in English
| WPRIM
| ID: wpr-241536
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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)-labeled 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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Phosphates
/
Asthma
/
Lymphocytes
/
Cell Differentiation
/
Cells, Cultured
/
Chemistry
/
Blotting, Western
/
Oligonucleotides, Antisense
/
RNA, Antisense
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Chinese Medical Journal
Year:
2011
Type:
Article
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