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

摘要

Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN,CLCA1, and SERPINB2. 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 MUC5AC and SPDEF 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 style="fixed-case">CS with style="fixed-case">IL‐13. style="fixed-case">POSTN, style="fixed-case">SERPINB2, and style="fixed-case">CLCA1 expression were measured 24 h after the last exposure to style="fixed-case">CS and style="fixed-case">IL‐13. In both models style="fixed-case">POSTN, style="fixed-case">SERPINB2, and style="fixed-case">CLCA1 expression were increased by style="fixed-case">IL‐13. style="fixed-case">CS markedly affected the style="fixed-case">IL‐13‐induced Th2 gene signature as indicated by a reduced style="fixed-case">POSTN, style="fixed-case">CLCA1, and style="fixed-case">MUC5 style="fixed-case">AC expression in both models. In contrast, style="fixed-case">IL‐13‐induced style="fixed-case">SERPINB2 expression remained unaffected by style="fixed-case">CS, whereas style="fixed-case">SPDEF expression was additively increased. Importantly, cessation of style="fixed-case">CS exposure failed to restore style="fixed-case">IL‐13‐induced style="fixed-case">POSTN and style="fixed-case">CLCA1 expression. We show for the first time that style="fixed-case">CS differentially affects the style="fixed-case">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.