Cigarette smoke differentially affects IL-13-induced gene expression in human airway epithelial cells.

Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of , , and This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2-high and Th2-low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL-13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin-related genes and in air-liquid interface differentiated human bronchial (ALI-PBEC) and tracheal epithelial cells (ALI-PTEC). Cultures were exposed to IL-13 for 14 days followed by 5 days of IL-13 with CS exposure. Alternatively, cultures were exposed once daily to CS for 14 days, followed by 5 days CS with IL-13. , , and expression were measured 24 h after the last exposure to CS and IL-13. In both models , , and expression were increased by IL-13. CS markedly affected the IL-13-induced Th2 gene signature as indicated by a reduced , , and expression in both models. In contrast, IL-13-induced expression remained unaffected by CS, whereas expression was additively increased. Importantly, cessation of CS exposure failed to restore IL-13-induced and expression. We show for the first time that CS differentially affects the IL-13-induced gene signature for Th2-high asthma. These findings provide novel insights into the interaction between Th2 inflammation and cigarette smoke that is important for asthma pathogenesis and biomarker-guided therapy in asthma.