Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.

中文翻译：

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焦炉排放物通过促进气道上皮细胞铁死亡而加剧过敏性哮喘


流行病学研究表明，焦炉排放物（COEs）会影响哮喘的恶化，但尚未得到实验结果证明。在这项研究中，我们首次发现 COE 会加剧小鼠模型中过敏原屋尘螨 (HDM) 诱发的过敏性哮喘。研究结果显示，与单独暴露组相比，COE+HDM联合暴露组的气道炎症、气道重塑和过敏反应加重。机制研究表明，COE + HDM 联合暴露组中铁和 MDA 水平较高，同时 GPX4 表达增加和减少。铁螯合剂去铁胺（DFO）在体外与 HDM 协同有效抑制 COE 诱导的铁死亡。进一步的研究强调了铁蛋白自噬在 COE + HDM 诱导的铁死亡中的作用。 3-甲基腺嘌呤 (3-MA) 可以抑制 COE + HDM 暴露组的铁死亡。有趣的是，我们给联合暴露组的小鼠腹腔注射DFO，发现DFO可以显着抑制COE加剧的铁死亡和过敏性哮喘。我们的研究结果将铁死亡与 COE 加剧的过敏性哮喘联系起来，这意味着铁死亡可能对职业接触 COE 的哮喘患者具有重要的治疗潜力。