# GPX4 alleviates airway inflammation by suppressing 5-LO expression and regulating ferroptosis

## TL;DR

This study shows that GPX4 reduces airway inflammation in asthma by suppressing 5-LO and preventing ferroptosis, suggesting it could be a new treatment target.

## Contribution

The novel contribution is identifying GPX4's role in mitigating asthma through suppression of 5-LO and regulation of ferroptosis.

## Key findings

- GPX4 reduces oxidative stress and ferroptosis markers in LPS-stimulated BEAS-2B cells.
- GPX4 inhibits ERK phosphorylation and 5-lipoxygenase (5-LO) expression.
- In asthmatic mice, GPX4 alleviates lung damage and inflammation.

## Abstract

Ferroptosis has been increasingly implicated in the pathophysiology of asthma. 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.

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.

The online version contains supplementary material available at 10.1186/s12931-026-03584-8.