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Glutathione peroxidase 4 (GPX4), the key enzymatic suppressor of ferroptosis, has a role in asthma that remains insufficiently defined. Here, we investigated the regulatory function of GPX4 in asthma airway epithelial cells using an OVA-induced murine model in conjunction with a lipopolysaccharide (LPS)-stimulated BEAS-2B cell system. Upregulation of GPX4 markedly reduced intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the accumulation of ferrous ions and other ferroptosis-related markers, while concomitantly alleviating mitochondrial abnormalities in LPS-stimulated BEAS-2B cells. GPX4 also inhibited ERK phosphorylation and downregulated 5-lipoxygenase (5-LO) expression. In OVA-induced asthmatic mice, GPX4 conferred significant protection, characterized by alleviated lung histopathological damage, reduced inflammatory responses, and attenuation of ferroptosis-associated alterations.<\/jats:p>\n                  <jats:p>These findings indicate that GPX4 mitigates asthma-related pathological changes primarily through suppression of 5-LO and modulation of ferroptosis-linked oxidative injury, highlighting GPX4 as a potential therapeutic target for asthma management.<\/jats:p>","DOI":"10.1186\/s12931-026-03584-8","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T01:13:41Z","timestamp":1771982021000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPX4 alleviates airway inflammation by suppressing 5-LO expression and regulating ferroptosis"],"prefix":"10.1186","volume":"27","author":[{"given":"Zehong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruimin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"issue":"10","key":"3584_CR1","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/S2213-2600(20)30363-5","volume":"8","author":"R EL-HUSSEINI Z W, GOSENS","year":"2020","unstructured":"El-Husseini Z W, Gosens R, Dekker F, et al. 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