Previous studies have indicated that
allergens such as house dust mites (HDM) in the environment can induce allergic
asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of
reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of
asthma remains to be elucidated. The present study used a HDM-induced mouse
asthma model to determine the effect of HDM exposure on allergic
asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic
asthma.
Airway hyperresponsiveness (AHR),
lung inflammation, mucus secretion,
IgE levels,
cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS levels,
glutathione (GSH) levels and changes in ferroptosis pathway
proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated
IgE levels in the BALF, lung
eosinophilia and a concomitant increase in
IL-13 and
IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of
glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that
protein expression levels of
acyl-CoA synthetase long-chain family member 4 and
15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway
inflammation, lipid peroxidation and ROS levels increased in HDM-induced
asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic
asthma.