title: Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression.
abstract: 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)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Diseases, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Xin-Rui
authors.initials: XR
authors.lastname: Tian
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Tian
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Bo
authors.forename: Shao-Gang
authors.initials: SG
authors.lastname: Li
authors.forename: Zhuo-la
authors.initials: ZL
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D016372:RNA, Antisense / Q000737:chemistry / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D010710:Phosphates; D016372:RNA, Antisense; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; C083120:phosphorodithioic acid