Coke oven emissions exacerbate allergic asthma by promoting ferroptosis in airway epithelial cells

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 Ptgs2 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.