Effects and mechanism of arsenic trioxide on reversing the asthma pathologies including Th17-IL-17 axis in a mouse model.

ABSTRACT

In traditional Chinese medicine, arsenous compounds, including arsenic trioxide (ATO), are often used to treat many diseases, which are safe and effective. Recently, studies have indicated that Th17- IL-17 involved in the pathogenesis and development of asthma. The goal of this study was to investigate the effect and mechanism of ATO on asthma, especially the Th17- IL-17 axis.We used oval bumin (OVA)-immunized mice as a model for asthma and treated mice with ATO or dexamethasone. The mice were then monitored airway responsiveness, airway inflammation, mucus production, IL-17 levels in BALF and the positive rate of Th17 cells. In vitro, CD4+ T cells from splenic cell suspensions were separated and purified. We measured the expression of IL-17 and caspase-12 protein in purified CD4+ T cells, and detected IL-17 levels in CD4+ T lymphocyte culture solution with or without ATO. Moreover, apoptosis, mitochondrial membrane potential, cytosolic calcium were analyzed. We found that ATO could reduce airway responsiveness, airway inflammation, mucus hyperplasia, the expression of IL-17 in BALF and the positive rate of Th17 cells at a level comparable to treatment with DXM. In vitro data suggested that ATO can induce CD4+ T cells apoptosis, cause mitochondrial dysfunction, Ca2+ overload and promote caspase-12 activation. Our study suggested that ATO had potential medical value for the treatment of human asthma..