Objective Asthma is a chronic airway heterogeneous disease and T-helper-type2(Th2) cells have an intimate connection with the pathogenesis of asthma by secreting IL-4, IL-5 and IL-13, recruiting eosinophils and mast cells, releasing IgE in the lungs and blood. Although it has been argued that androgen and estrogen are involved in asthma progression, how they affect asthma is unknown. Studies showed that Runx3 could promote the migration of naïve CD4+ T cells to Th1 cells and inhibit the production of IL-4 and accelerate the expression of IFN-γ. Hence, the aim of our study was to explore how androgen and estrogen regulation asthma by interacting with Runx3.
Materials and methods Clinical assessment and pulmonary function tests were conducted on 35 patients with confirmed asthma, and peripheral blood was collected. At the same time, peripheral blood was obtained from 21 normal controls. Female C57BL/6 mice and bronchial epithelial cells (BECs) were used to develop asthma mouse models and asthma vitro models respectively. Western blotting, flow cytometry and immunohistochemistry were utilized to detect Th1 and Th2 cells differentiation and Runx3 expression. Enzyme-linked immunosorbent assay was used for the concentrations of androgen, estrogen, IL-4 and IFN-γ.
Results Serum DHT levels were considerably decreased in asthma patients compared to normal controls, while serum estradiol levels were significantly increased in asthma patients compared with normal controls. The murine model of asthma was established successfully. The principal manifestations were increased total cells and eosinophils in BALF, IL-4 in mice supernatant and activated Th2 cell differentiation. In asthmatic mice and asthma vitro models treated with androgen combined with estrogen, expressions of Runx3 and T-bet in lung tissues were significantly increased, while the corresponding expression of GATA3 was significantly decreased. Meanwhile, Th1 cells increased markedly increased and the corresponding Th2 cells decreased markedly.
Conclusions These findings suggest that androgen combination estrogen may improve asthma and provide a viable treatment. However, further implementation needs more research.