Identification of functional roles and therapeutic targets of the STAT pathway in PM-induced allergic rhinitis.

BACKGROUND

Increasing evidence suggests that exposure to fine particulate matter (PM) is associated with an elevated risk of respiratory diseases. However, the precise mechanisms by which PM influences inflammatory processes in allergic rhinitis (AR) remain insufficiently understood. The STAT pathway has been identified as a critical mediator of immune and inflammatory responses, but its specific role in modulating PM-induced effects in the nasal mucosa of AR remains unclear. This study aims to investigate the impact of PM on the STAT pathway in the inflammatory response of the nasal mucosa during AR.

METHODS

We analyzed mRNA expression profiles (GSE215411) from the Gene Expression Omnibus (GEO) database to investigate the effects of PM on human nasal mucosa-derived fibroblasts. Differential expression analysis identified differential expression genes (DEGs), which were visualized through hierarchical clustering and radar plots. GO/KEGG enrichment and Gene Set Enrichment Analysis (GSEA) identified key pathways, focusing on STAT pathway enrichment. Protein-protein interactions (PPIs) within the STAT pathway were analyzed using STRING and Cytoscapedatabase, revealing immune response and cytokine signaling as predominant functional pathways. An AR model, induced by ovalbumin sensitization and whole-body ambient PM exposure, was utilized to assess the activation of the STAT pathway in nasal mucosal tissue.

RESULTS

A total of 426 DEGs were identified in human nasal mucosa-derived fibroblasts following PM exposure, emphasizing STAT pathway involvement. Validation in an AR mouse model confirmed that allergens and PM activate the STAT pathway, modulating Th2 and inflammatory cytokines.

CONCLUSION

PM exposure significantly activates the STAT pathway in the nasal mucosa of AR, amplifying Th2-related inflammatory cytokine response.