The role of IL-25 in the reduction of oxidative stress and the apoptosis of airway epithelial cells with specific immunotherapy in an asthma mouse model.

Oxidative stress and cell apoptosis play important roles in the pathogenesis of asthma. Specific immunotherapy (SIT) is the only curative approach for asthma and is effective at decreasing asthmatic oxidation and cell apoptosis, but the mechanisms remain unclear. In this study, by using in vivo and in vitro models, we indirectly demonstrated that SIT alleviated the apoptosis and oxidative stress of bronchial epithelial cells in an asthma model through regulating interleukin (IL)-25. Female BALB/c mice were used for an asthma model induced by exposure to house dust mite (HDM) extracts as allergens. Prior to the challenge, the mice were either given the SIT vaccine or N-Acetyl-L-cysteine (NAC).

resultsCompared with that in asthma models, SIT administration decreased (1) airway hyper-responsiveness; (2) the production of cytokines, including IL-4, IL-5, IL-13, and IL-25, as well as serum HDM-specific IgE and IgG1, as shown by ELISA; and (3) lipid oxidative species, such as reactive oxidative species (ROS) and malondialdehyde (MDA), in the lung tissue. Moreover, TUNEL staining showed that SIT alleviated pulmonary cell apoptosis. In vitro, flow cytometry showed that human recombinant IL-25 (rIL-25) led to increased cell apoptosis and ROS in the human epithelial cell line 16HBE in a dose and time-dependent fashion. In conclusion, in vivo, SIT reduced asthmatic Th2 cytokine levels and the production of IL-25 and alleviated oxidative stress and cell apoptosis in the lung tissue. In vitro, IL-25 increased the number of apoptotic cells and the production of ROS in16HBE cells.