Effect Of BCG On Expression Of T Cell-specific Transcription Factors T-bet And GATA-3 In Asthmatic Mice

Background: The bronchial asthma is a chronic airway inflammatory disease in which eosinophils, mast cells and T lymphocytes and other inflammatory cells and cellular element play a role. Study confirmed that the incidence of bronchial asthma and the Thl/Th2 imbalance are closely related, Th2 cell activation hypersplenism are an important of asthma pathogenesis. At present, the treatment of asthma focus has been from pure anti-respiratory tract spasm shifted to anti-inflammatory treatment, especially how to promote TH0 cells into Th1-type transformation, inhibiting Th2 cells thereby control the development of asthma. Available information found that a variety of transcription factors or cell signaling pathways relate with Th cell differentiation. Of which transcription factors GATA-3 and T-bet playing an important role. Some people think that the balance between T-bet and GATA-3 decides the fate of T cells in the mucosal immune fate . also the balance of Th1/Th2 the stability. Bacillus Calmette-Guerin (BCG) as a non-specific immune response modifier, can suppress Th2 immune response and induce Th1 immune response, reduce airway inflammatory response.. But it hasn't been reported that whether BCG can regulate transcription factor T-bet and GATA-3 balance to alleviate airway inflammation so far.Objective: Through the establishment of mouse asthma model, mice were give to the prevention and treatment of BCG vaccination, Observation effect of BCG on expression of T cell-specific transcription factors T-bet and GATA-3 in asthmatic mice and compare the differences of the prevention and treatment of vaccination, and explore the new treatment mechanism about asthma treated with BCG.Methods: 32 male Kunming mice were randomly divided into four groups:normal control group (A group), asthma model group (B group), BCG prevention group (C group), BCG treatment group (D group).We establish the asthma model of mice by sensitizing with ovalbumin. Obesrving the general situation of four groups mice; Detected cell types in BALF,analyzed pathological changes in lungs; Expressions of T-bet and GATA-3 protein were measured with the way of half-ration of immunohistochemistry in lung tissues of mice.Results:1. BALF examination revealed:Number of total leukocytes and eosinophil proportion in BALF of asthma model group (B group) was significantly higher than normal control group (A group) (P<0.01 ) . Number of total leukocytes and eosinophil proportion in BALF of BCG prevention group (C group) and BCG treatment group (D group) were significantly lower than asthma model group (B group) (P<0.01 ), There was no significantly difference between BCG prevention group (C group) and BCG treatment group (D group) (P>0.05).2. Pathological examination revealed :Pathological analysis of the lung showed that normal control group (A group) almost no inflammatory cell infiltration, and asthma model group (B group) a large number of inflammatory cells and infiltration, was significantly higher than normal control group (A group) (P<0.01 ).Two BCG groups had lower inflammatory cells and infiltration than asthma model group (B group)(P<0.01) ,but higher than normal control group (A group) (P<0.01) .3. Immunohistochemical results revealed: Expressions of T-bet in asthma model group (B group) were significantly lower than in normal control group (A group) (P<0.01) .The difference was also significantly when BCG prevention group (C group) or BCG treatment group (D group) was in contrast with normal control group (A group) (P all<0.01) . In contrast with asthma model group (B group) expressions of T-bet in BCG prevention group (C group) were significantly higher (P<0.01) . The difference was also significantly when BCG treatment group (D group) was in contrast with asthma model group (B group) (P<0.01) .There was no significantly difference between BCG treatment group (D group) and BCG prevention group (C group) (P>0.05). Expressions of GATA-3 in asthma model group (B group) were significantly higher than in normal control group (A group) (P<0.01) .The difference was also significantly when BCG prevention group (C group) or BCG treatment group (D group) was in contrast with normal control group (A group) (P all<0.01). In contrast with asthma model group (B group)expressions of GATA-3 in BCG prevention group (C group)were significantly lower (P<0.01). The difference was also significantly when BCG treatment group (D group) was in contrast with asthma model group (B group) (P<0.01) .There was no significantly difference between BCG treatment group (D group) and BCG prevention group (C group) (P>0.05).4.The analysis of Correlation indicated that expressions of T-bet was a significant negatively correlation with the airway inflammation and BALF eosinophil percentage in asthma model group (B group)(P all<0.01); expressions of GATA-3 was a significant positively correlation with the airway inflammation and BALF eosinophil percentage in asthma model group (B group) (P all<0.05);Expressions of T-bet was a significant negatively correlation with expressions of GATA-3 in asthma model group (B group) (P<0.01).Conclusion: 1.Successful created the mouse asthma model through sensitized and challenged with OVA. In bronchial asthma model, The imbalance T cell-specific transcription factors T-bet and GATA-3 contributes to both low expression of T-bet and high expression of GATA-3. Expressions of T-bet was negatively correlation with airway inflammation, expressions of GATA-3 was positively correlation with airway inflammation. Imbalance of transcription factors T-bet and GATA-3 may play a key role in the formation of airway inflammation of asthma. 2. BCG can reduce the asthma airway inflammation, increase the protein expression of transcription factor T-bet and reduce the protein expression of transcription factor GATA-3 at the same time. So BCG treatment can correct Th1/Th2 imbalance through increase the differentiation of T helper cell 1 and inhibit the overdifferentiation of T helper cell 2.