Environmental allergens house dust mite‑induced asthma is associated with ferroptosis in the lungs

Tang,Weifeng; Dong,Ming; Teng,Fangzhou; Cui,Jie; Zhu,Xueyi; Wang,Wenqian; Wuniqiemu,Tulake; Qin,Jingjing; Yi,La; Wang,Shiyuan; Dong,Jingcheng; Wei,Ying

doi:10.3892/etm.2021.10918

Environmental allergens house dust mite‑induced asthma is associated with ferroptosis in the lungs

Authors:
- Weifeng Tang
- Ming Dong
- Fangzhou Teng
- Jie Cui
- Xueyi Zhu
- Wenqian Wang
- Tulake Wuniqiemu
- Jingjing Qin
- La Yi
- Shiyuan Wang
- Jingcheng Dong
- Ying Wei
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Affiliations: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Acupuncture and Orthopedics, Gumei Community Health Center, Shanghai 201102, P.R. China
Published online on: October 26, 2021 https://doi.org/10.3892/etm.2021.10918
Article Number: 1483
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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