| Background and Objective:Asthma is one of common diseases of respiratory system and its mechanism remains to be unclear. It is believed that asthma is related with many factors such as inheritance, immune regulation and environment. With the research in asthma, more and more evidences show imbalance of Thl/Th2 maybe contributes to asthma. In the course of naive Th cells differentiating into Th1 or Th2 cells , the interaction between some special transcription factors is required. The two newly found transcription factors, T-bet and GATA3, were believed to play a key role in the course. T-bet, a member of the T-box family of transcription factors, is a key controller of Th1 differentiation. T-bet expression is specifically up-regulated in naive Th cells that differentiate along the Th1 pathway, meanwhile, transcription factor T-bet can also inhibit the expression of GATA3 which promotes the Th1 dominant response. GATA3, a member of the GATA-binding family of zinc-finger transcription factors, has been identified as a key regulator of Th2 development. GATA3 can also act through signal transducer and activator of transcription 4 (Stat4) and downregulate IL-12 receptor (32 chain (IL-12Rp2) to suppress Th1 differentiation. In patients of asthma, the number of Th2 cells rises which makes humoral immunity predominance. B cells change into plasma cells which produce large amount of IgE and cause chronic inflammation in bronchus. Specific immunotherapy(SIT) is recommended by WHO, and is the only treatment to origin of asthma. Although specific immunotherapy has been used since 1911 by Noon and Freeman for allergic disorders, its value in the treatment of asthma continues to be debated despite numerous studies that have demonstrated its efficacy. This study aims to investigate the effect of T-bet and GATA3 in SIT treated children with allergic asthma and provide the theory support for the new treatment method or medicine for asthma.Methods: Thirty-six patients with allergic asthma (19 men and 17 women) were from pediatrics clinic service in the first affiliated hospital of Zhengzhou University who had the typical symptoms and medical records of asthma and fulfilled the criteria of allergic asthma. The mean age of patients is 12.5 years old (range from 6 to 14). They were divided into 0 week, 15 weeks and 51 weeks three groups, each group contained 12 patients. All of them were positive in skin test of Derp 1 (ALK, Danmark) and given a 51-week course of immunotherapy with Dermatophagoides pteronyssinus extract (Alutard Der p, ALK-Abello, Horsholm, Denmark). PBMCs were obtained at weeks 0, 16 and 51 of specific immunotherapy treatment. RNA was isolated from PBMC samples and stored in -80℃.After being completed the sample collection, all RNA were reverse transcribed to cDNA. T-bet and GATA3 in PBMCs were detected by real-time RT-PCR. The results were analyzed using the 2-ΔΔct method.Results: With the development in SIT, the magnitude of T-bet mRNA expression normalised to p-actin was 2.96-fold in 16 weeks than that in 0 week,and was 0.35-fold than that in 51 weeks. The magnitude of GATA3 mRNA expression normalised top-actin was 0.75-fold in 16 weeks than that in 0 week,and was 0.09-fold than in 51 weeks.The magnitude of T-bet mRNA expression versus GATA3 rises gradually, the ratio was 3.78 higher in 16 weeks than in 0 weeks, and 4.69 higher in 51 weeks than in 0 weeks.Conclusions:1. This study show the magnitude of T-bet mRNA expression versus GATA3 increased in PBMCs during the treatment of SIT, indicate transcription factors T-bet and GATA3 could play an important role in asthma and specific immunotherapy.
|
PDF Full Text Request