[Imbalanced T cell-specific transcription factors T-bet and GATA-3 and relationship to airway inflammation in asthmatic rats].

OBJECTIVE

To identify the change of the mRNA and protein expression of T-bet and GATA-3 in lung tissues, and to investigate the association between the imbalanced T cell-specific transcription factors T-bet/GATA-3 and the airway inflammation in asthmatic rats.

METHODS

Twenty-four male SD rats were randomly divided into a control group and an asthmatic group. Airway responsiveness was measured and the change of airway histology was observed. The concentrations of interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in the lungs were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.

RESULTS

The expiration resistance after injection of acetylcholine chloride (20, 40, 80, 160 microg/ml) in the asthmatic group was (6.26 +/- 0.85), (11.55 +/- 3.09), (28.74 +/- 5.94), (3,710.83 +/- 197.49) cm H2O.ml(-1).s(-1) respectively; and that in the control group was (1.51 +/- 0.18), (2.15 +/- 0.36), (6.08 +/- 1.06), (37.17 +/- 6.12) cm H2O.ml(-1).s(-1) respectively; the difference being significant between the two groups (all P < 0.01). In the asthmatic group, the numbers of eosinophils and lymphocytes, the thicknesses of WA/Pi and ASM/Pi were (26.0 +/- 1.6)/mm(2), (45.2 +/- 3.2)/mm(2), 12.0 +/- 1.4, 6.7 +/- 0.6, respectively; and those of the control group were (2.9 +/- 1.2)/mm(2), (8.8 +/- 1.8)/mm(2), 6.4 +/- 0.8, 2.7 +/- 0.5, respectively; all were significantly different between the two groups (all P < 0.01). In the asthmatic group, the concentrations of IL-4, IL-5, and IFN-gamma in BALF were (23.4 +/- 0.7) pg/ml, (24.8 +/- 0.5) pg/ml, (21.7 +/- 1.1) pg/ml, respectively, and those of the control group were (9.3 +/- 0.3) pg/ml, (12.5 +/- 0.3) pg/ml, (65.8 +/- 2.1) pg/ml, respectively; all were significantly different between the two groups (all P < 0.01). In the control group, the mRNA ratio of T-bet to GATA-3 (0.73 +/- 0.32) was significantly increased compared with the asthmatic group (0.06 +/- 0.09, P < 0.01). There was also a significant difference in the ratio of protein expression of T-bet to GATA-3 between the control group (0.75 +/- 0.25) and the asthmatic group (0.09 +/- 0.04, P < 0.01). The ratio of protein expression of T-bet and GATA-3 was correlated negatively with expiration resistance (r = -0.959, -0.919, -0.949, all P < 0.01), the numbers of eosinophils and lymphocytes in lung tissues (r = -0.832, -0.831, all P < 0.01), the thicknesses of WA/Pi and ASM/Pi (r = -0.837, -0.863, all P < 0.01) and the concentrations of IL-4, IL-5 in BALF (r = 0.921, 0.920, all P < 0.01), the mRNA of IL-4, IL-5 in lung tissues (r = -0.964, -0.931, all P < 0.01), but positively with the concentrations of IFN-gamma in BALF and the mRNA of IFN-gamma in lung tissues (r = -0.934, 0.983, all P < 0.01).

CONCLUSION

Imbalance of transcription factors T-bet and GATA-3, a reflection of the immune imbalance in asthma, may play a key role in the formation of airway inflammation in the disease.