Synergistic Induction of Neutrophilic Inflammatory Programs by Staphylococcus aureus and Cigarette Smoke in Airway...

Staphylococcus aureus (SA) colonization and cigarette smoking are both implicated in the pathogenesis of chronic airway disease, yet their combined effects on epithelial responses remain unclear. We investigated transcriptomic changes in human bronchial epithelial cells (BEAS-2B) following co-exposure to SA and cigarette smoke extract (CSE). RNA sequencing revealed that combined SA+CSE co-exposure was associated with a marked increase in differentially expressed genes, compared with single exposures. Functional enrichment and network analyses identified significant activation of pathways related to neutrophil migration, extracellular matrix remodeling, and inflammatory cascades, including TNF and IL-17 signaling. Key hub genes, notably CCL20, CXCL1, CXCL8, and IL-24, showed marked synergistic upregulation, which was validated by quantitative RT-PCR. These findings suggest that SA and cigarette smoke co-exposure is associated with a transcriptomic profile suggestive of neutrophilic inflammation. The involvement of IL-24 and IL-17 signaling suggests potential pathways linking bacterial colonization and smoking to airway inflammation and remodeling.