Restoration of glucocorticoid receptor expression by sterol-enriched Sargassum horneri attenuates particulate matter-induced epithelial stress and surfactant transcriptional alterations in alveolar type II epithelial cells

Ambient particulate matter (PM) disrupts alveolar epithelial integrity by inducing oxidative stress and inflammatory signaling. While Sargassum horneri has been reported to protect against PM-associated airway injury, whether its sterol-enriched fraction contributes to glucocorticoid receptor (GR)-associated epithelial regulation has not been investigated. Here, we show that a sterol-enriched Sargassum horneri ethanol extract (S-SHE) contained the highest level of fucosterol among the solvent-partitioned fractions and attenuated PM-induced cytotoxicity. In PM-exposed MLE-12 cells, S-SHE reduced intracellular ROS generation, malondialdehyde levels, and surface accumulation of Al and Fe, and alleviated PM-induced morphological alterations. S-SHE also suppressed TLR2/MyD88/TRAF6-associated inflammatory signaling, NF-κB transcriptional activity, and the expression of pro-inflammatory cytokines and chemokines. Notably, S-SHE restored GR expression and modulated surfactant-related gene expression, including Sftpb and Sftpc . These results suggest that sterol-enriched components of Sargassum horneri attenuate PM-induced epithelial stress and may have potential relevance to corticosteroid-related epithelial regulation.