Abstract
Background: Studies have indicated that allergens such as house dust mites (HDM) in the environment could induce allergic asthma. Ferroptosis is a newly discovered regulatory cell death characterized by aberrant lipid peroxidation and accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological progress of asthma remains to be elucidated. In this study, we used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and the underlying mechanisms. Methods: Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation and mucus secretion, IgE and cytokine levels as well as inflammatory cell counts in bronchalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS, glutathione (GSH) levels and changes in ferroptosis pathway proteins in the lung were also determined. Results: HDM exposure increased AHR significantly, and enhanced inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE level in BALF, lung eosinophilia, and a concomitant increase in IL-13 and IL-5 in BALF were observed. HDM inhalation increased ROS and decreased GSH level in the lung. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blot analysis demonstrated that activity of glutathione peroxidase 4 (GPX4) and catalytic subunit solute carrier family 7 member 11 (SLC7A11) decreased significantly, and protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and 15 Lipoxygenase 1 (15-LO1) upregulated prominently compared with mice in normal control group. Conclusions: These in all indicated that the AHR, airway inflammation, lipid peroxidation and ROS level increased in HDM-induced asthma, and HDM inhalation caused ferroptosis in the lungs, which helped to form a better understanding of the pathogenesis of allergic asthma and targeted treatment strategies.
Environmental Allergens House Dust Mites-induced Asthma Causes Ferroptosis in the Lungs
