| Background:Asthma is a chronic inflammatory disorder of the airways in which many cells(such as mast cells,eosinophils,T lymphocytes,dendritic cells and neutrophils) and cellular elements play a role.It has been documented that the imbalance of Th1/Th2 and the incidence of asthma are closely related.Present findings suggest that there are many transcription factors taking part in the differentiation of Th cells into Th1 or Th2 cells,of which,it is believed that transcription factor T-bet and GATA-3 are of greatest importance.The critical roles for T-bet and GATA-3 protein in regulation of Th1 and Th2 lineage-associated cytokine genes have been well documented.Recent work shows that they are critical for Th1 and Th2 polarization and therefore are very important of the pathogenesis of brochial asthma.As we all known,inhaled glucocorticosteroids(ICS) are currently the most effective anti-inflammatory medications for the treatment of bronchial asthma.Studies have demonstrated their efficacy in reducing asthma symptoms,improving quality of life,improving lung function, decreasing airway hyperresponsiveness,controlling airway inflammation, reducing frequency and severity of exacerbations,and reducing asthma mortality.However,very little is known about the mechanisms through which inhaled glucocorticosteroids controlling bronchial asthma. Objective:To observe the effect of inhaled glucocorticosteroids on expression of T cell-specific transcription factor T-bet and GATA-3 in asthmatic mice,and explore the new treatment mechanism about asthma treated with ICS.Methods:24 male Kunming mice were divided into three groups randomly:normal control group(Group A),asthma model group(Group B),inhaled glucocorticosteroids treated group(Group C).Asthma model were established by sensitizing mice with ovalbumin.The general situation of three groups were observed,cell types in BALF were detected,pathological changes in lung tissues were analyzed and expressions of T-bet and GATA-3 protein were measured with the way of immunohistochemistry in lung tissues.Results:1.BALF examination revealed:Number of total leukocytes and eosinophil proportion in BALF of asthma model group(Group B) were significantly higher than normal control group(Group A)(P＜0.01).Number of total leukocytes and eosinophil proportion in BALF of ICS treated group(Group C) were significantly lower than asthma model group(Group B)(P＜0.01).2.Lung tissue pathological examination revealed:Lung tissue of normal control group(Group A) had no inflammatory cell infiltration,while Lung tissue of asthma model group(Group B) had severe inflammatory cell infiltration,which was significantly more severe than normal control group(Group A)(P＜0.01).Lung tissue of ICS treated group(Group C) had milder inflammatory cell infiltration than asthma model group(Group B)(P＜0.01),but still more severe than normal control group(Group A)(P＜0.01).3.Immunohistochemical results revealed:Expression of T-bet protein in asthma model group(Group B) and ICS treated group(Group C) were significantly lower than that in normal control group(Group A)(P＜0.01).However,there was no significant difference between ICS treated group(Group C) and asthma model group(Group B)(P＞0.05).Expression of GATA-3 protein in asthma model group(Group B) and ICS treated group(Group C) were significantly higher than that in normal control group(Group A)(P＜0.01).The difference was also significant when ICS treated group(Group C) contrasted with asthma model group(Group B)(P＜0.01).4.The analysis of Correlation revealed:The analysis of Correlation indicated that T-bet protein expression was a significant negative correlation with airway inflammation and BALF eosinophil proportion(P＜0.01);GATA-3 protein expression was a significant positive correlation with airway inflammation and BALF eosinophil proportion in asthma model group(Group B)(P＜0.05); Expression of T-bet protein was a significant negative correlation with expression of GATA-3 protein in asthma model group(Group B)(P＜0.01).Conclusion:1.Successfully created the mouse asthma model through sensitizing with OVA.2.In bronchial asthmatic model,the imbalance of T cell-specific transcription factor T-bet and GATA-3 contributes to both lower expression of T-bet and higher expression of GATA-3.Expression of T-bet protein was a negative correlation with expression of GATA-3 protein.Expression of T-bet was a negative correlation with airway inflammation while expression of GATA-3 was a positively correlation with airway inflammation.Imbalance of transcription factor T-bet and GATA-3 may play a key role in formation of airway inflammation of asthma.3.ICS can reduce asthma airway inflammation,reduce the expression of transcription factor GATA-3,but cannot increase the expression of transcription factor T-bet.So ICS may not increase the expression of transcription factor T-bet and reduce the over expression of transcription factor GATA-3 at the same time when used in treating asthma airway inflammation.
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