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; Liu, Yi; Wang, Shiyuan; Dong, Jingcheng; Wei, Ying

doi:10.3892/etm.2021.10918

Cited by 33 publications

(19 citation statements)

References 59 publications

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“…47 A recent study has shown that environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs, and the effect of agonists and inhibitors of ferroptosis on airway inflammation in HDM-induced asthma also requires further study. 48 In our in vivo experiment, we found that HDM-induced mice treated with ferroptosis inhibitors (DFO and Fer-1) had decreased IL-4, IL-5 and IL-13 expression levels. The results indicated that inhibition of ferroptosis reduced type 2 airway inflammation in asthma.…”

Section: Discussionmentioning

confidence: 63%

“…Type 2 inflammation is an important disease mechanism in a large subgroup of individuals with asthma, and type 2 cytokines provided multiple potential therapeutic targets for asthma 47 . A recent study has shown that environmental allergens house dust mite‐induced asthma is associated with ferroptosis in the lungs, and the effect of agonists and inhibitors of ferroptosis on airway inflammation in HDM‐induced asthma also requires further study 48 . In our in vivo experiment, we found that HDM‐induced mice treated with ferroptosis inhibitors (DFO and Fer‐1) had decreased IL‐4, IL‐5 and IL‐13 expression levels.…”

Section: Discussionmentioning

confidence: 99%

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HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

et al. 2022

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Asthma is a disease characterized by airway epithelial barrier destruction, chronic airway inflammation, and airway remodeling. Repeated damage to airway epithelial cells by allergens in the environment plays an important role in the pathophysiology of asthma. Ferroptosis is a novel form of regulated cell death mediated by lipid peroxidation in association with free iron‐mediated Fenton reactions. In this study, we explored the contribution of ferroptosis to house dust mite (HDM)‐induced asthma models. Our in vivo and in vitro models showed labile iron accumulation and enhanced lipid peroxidation with concomitant nonapoptotic cell death upon HDM exposure. Treatment with ferroptosis inhibitors deferoxamine (DFO) and ferrostatin‐1 (Fer‐1) illuminated the role of ferroptosis and related damage‐associated molecular patterns in HDM‐treated airway epithelial cells. Furthermore, DFO and Fer‐1 reduced HDM‐induced airway inflammation in model mice. Mechanistically, NCOA4‐mediated ferritin‐selective autophagy (ferritinophagy) was initiated during ferritin degradation in response to HDM exposure. Together, these data suggest that ferroptosis plays an important role in HDM‐induced asthma and that ferroptosis may be a potential treatment target for HDM‐induced asthma.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

et al. 2022

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“…Studies have reported that IL13 is associated with mitochondrial dysfunction in patients with sialadenitis [ 14 ] and protects the mitochondria of cardiomyocytes in patients with septicemia [ 13 ]. Increased IL13 expression has been reported in the dysfunctional mitochondria of mice with house dust mite-induced asthma [ 17 ]. IL13 has been reported to increase the glucose tolerance and mitochondrial activity of the muscles after exercise [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL13 frequently accompanies mitochondria-related conditions, including in infectious disease [ 13 ], inflammatory diseases [ 14 ], and metabolic diseases [ 15 ] and even in cancers [ 16 ]. IL13 has also been reported to be associated with mitochondrial dysfunction in an animal-induced asthma model [ 17 ]. The relationship between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines, including IL13, was also investigated in knee osteoarthritis [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

IL13 Promoter (−1055) Polymorphism Associated with Leukocyte Mitochondria DNA Copy Number in Chronic Obstructive Pulmonary Disease

Liu

Chang

et al. 2022

Cells

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IL13 polymorphism is associated with chronic obstructive pulmonary disease (COPD). Patients with COPD have smaller numbers of mitochondria deoxyribonucleic acid copies (mtDNA-CN) than people without COPD do. However, whether IL13 polymorphism affects the mutation and recombination of mitochondria remains unclear. Data for patients with COPD and non-COPD were collected from Kaohsiung Chang Gung Memorial Hospital to enable a comparison of their leukocyte mtDNA-CN and the association of this information with IL-13 promoter (−1055) polymorphism. This study included 99 patients with COPD and 117 individuals without COPD. The non-COPD individuals included 77 healthy individuals that never smoked and 40 healthy smokers. The patients with COPD exhibited significantly lower mtDNA-CN than non-COPD did (250.34 vs. 440.03; p < 0.001); mtDNA-CN was particularly pronounced in individuals with the IL13 CC and CT genotypes compared with individuals with the TT genotype. When only individuals without COPD were considered and when all participants were considered, the differences in the mtDNA-CNs in individuals with the CC and CT genotypes were more significant than those in individuals with the TT genotype (448.4 and 533.6 vs. 282.8; p < 0.05 in non-COPD group); (368.8 and 362.6 vs. 249.6, p < 0.05 in all participants). The increase mtDNA-CN in the CC and CT genotypes was also more than that in the TT genotype in COPD patients, but showed no significance (260.1 and 230.5 vs. 149.9; p = 0.343). The finding shows that COPD is a mitochondria regulatory disorder and IL-13 promoter (−1055) polymorphism is associated with leukocyte mtDNA-CN. Developing COPD control methods based on mitochondrial regulation will be possible.

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“…Ferroptosis was involved in the development and progression of a variety of lung diseases, including acute lung injury, COPD, and asthma [ 29 – 31 ]. Yoshida et al [ 32 ] investigated the involvement of ferroptosis in the development and progression of COPD both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

The role of ferroptosis in chronic intermittent hypoxia-induced lung injury

et al. 2022

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Purpose Chronic intermittent hypoxia (CIH) causes lung injury but the mechanism is unclear. Ferroptosis is a novel form of programmed cell death. In this research, we attempted to explore the role of ferroptosis in CIH-induced lung injury both in vitro and in vivo. Methods Sprague-Dawley rats were randomly separated into control group, CIH group and CIH + ferrostatin-1 group (CIH + Fer-1). Rats in the CIH group and CIH + Fer-1 group were exposed to intermittent hypoxia for 12 weeks. Human bronchial epithelial cell line (BEAS-2B) was cultivated for 24 h in either conventional culture medium or under CIH conditions. Fer-1 was applied to observe its treatment effects. Histological changes were evaluated by Hematoxylin–eosin (HE) staining and masson staining. The expression levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) were detected via qRT-PCR or Western blot. Cell counting kit-8 (CCK-8) was used to assess cell viability. The apoptotic rate and reactive oxygen species (ROS) was calculated by flow cytometry. Results Histology showed that CIH treatment induced lung injury and pulmonary fibrosis in lung tissue. After Fer-1 treatment, the pathological changes caused by CIH alleviated. The mRNA and protein levels of GPX4 decreased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA and protein levels of ACSL4 increased significantly in lung tissues of CIH-treated rats and BEAS-2B, (p < 0.05). The mRNA levels of IL-6 and TNFα in BEAS-2B increased after CIH treatment, (p < 0.05). Cell viability decreased, apoptosis rate and ROS increased in CIH-treated BEAS-2B, (p < 0.05). Cotreatment with Fer-1 reversed CIH-induced apoptosis, cell viability, ROS accumulation, mRNA and protein levels of GPX4, ACSL4, IL-6 and TNFα both in vitro and in vivo (p < 0.05). Conclusions Ferroptosis occurred in CIH-induced lung injury, both in vitro and in vivo. The ferroptosis inhibitor Fer-1 alleviated cell injury and ferroptosis in CIH-treated BEAS-2B and lung tissues of rats.

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

Cited by 33 publications

References 59 publications

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

IL13 Promoter (−1055) Polymorphism Associated with Leukocyte Mitochondria DNA Copy Number in Chronic Obstructive Pulmonary Disease

The role of ferroptosis in chronic intermittent hypoxia-induced lung injury

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