Effects Of STAT6 Decoy Oligonucleotides On Eotaxin Expression In Mice Models Of Asthma

Abstract:objective:Bronchial asthma is a chronic airway inflammatory disease with eosinophil (EOS)infiltration.The accumulated EOS in airway plays a central role in asthma. The sustained activation and over-expression of signal transduction and activator of transcription 6(STAT6) promote the predominantly expression of Th2 cells and induce the activation of chemotactic factor such as Eotaxin,gather the EOS into airway,induce the inflammation and hyperresponsiveness of airway. This study was to observe the influence of STAT6 decoy Oligonucleotides on the Eotaxin Protein,their mRNA expresstion and the EOS WBC LYM numbers in BALF,observe the effect of the STAT6 decoy ODN on the inflammation of asthma mice.Methods:32 BALB/C female mice were randomly divided into four groups:normal control group (N), asthmatic group(A),STAT6 decoy asthmatic group(ST-ODN) and scrambled ODN asthma group(SC-ODN),there were eight mice in each groups;The asthmatic models of BALB/C mice were established by immunized with ovalbumin(OVA); The STAT6 decoy ODN and scrambled ODN were respectively transfered to the ST-ODN group and SC-ODN group by local administration;The number of white blood cells,eosinophils and lymphocytes in branehoalveolar lavage fluid was measured by microscope;Pathological changes were observed by HE staining;The lungs were used for frozen section, the distribution of FITC ODN in lung tissue Frozen sections was observed by fluorescence microscope.The mRNA of Eotaxin and the protein expression in airway epithelium were detected by reverse transeription polymerase chain reactin (RT-PCR) and immunohistochemistry respectively. Results:1.The lung tissue with FITC-ODN administration were directly observed by frozen section with fluorescence microscope and the green fluorescence was found in lung tissue especially in the epithelial cells.2.White blood cells,lymphocytes, eosinophils in the branehoalveolar lavage fluid of ST-ODN group were significantly lower than those in the asthmatic group(P<0.05),while There were no significant differences (P>0.05)between the SC-ODN group and asthmatic group.3.The mRNA and protein expression of Eotaxin in normal group were significantly lower than those in asthmatic group(P<0.01).The mRNA and protein expression of Eotaxin in ST-ODN group was obviously lower than those in asthmatic group,while there was no significant difference (P>0.05)in the Eotaxin protein and mRNA expression between the SC-ODN group and asthmatic group.Conclusion:STAT6 decoy ODN were absorbed into the airway epithelial cells by local administration,which significantly inhibited the expression of Eotaxin protein and mRNA in lung tissues, decreased the white blood cells,lymphocytes and eosinophils of asthmatic mice in the BALF. Therefore reduced the airway inflammation.