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

Mertens, T. C. J., van der Does, A. M., Kistemaker, L. E., Ninaber, D. K., Taube, C. & Hiemstra, P. S., Jul-2017, In : Physiological Reports. 5, 13, 13 p., e13347.

Research output: Contribution to journalArticleAcademicpeer-review

  • Tinne C J Mertens
  • Anne M van der Does
  • Loes E Kistemaker
  • Dennis K Ninaber
  • Christian Taube
  • Pieter S Hiemstra

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 CS with IL-13. POSTN, SERPINB2, and CLCA1 expression were measured 24 h after the last exposure to CS and IL-13. In both models POSTN, SERPINB2, and CLCA1 expression were increased by IL-13. CS markedly affected the IL-13-induced Th2 gene signature as indicated by a reduced POSTN, CLCA1, and MUC5AC expression in both models. In contrast, IL-13-induced SERPINB2 expression remained unaffected by CS, whereas SPDEF expression was additively increased. Importantly, cessation of CS exposure failed to restore IL-13-induced POSTN and CLCA1 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.

Original languageEnglish
Article numbere13347
Number of pages13
JournalPhysiological Reports
Issue number13
Publication statusPublished - Jul-2017


  • Journal Article, BRONCHIAL EPITHELIUM, ASTHMA, interleukin 13, primary human epithelial cells, whole cigarette smoke, T helper 2, INFLAMMATION, Exposure, Mice, LEBRIKIZUMAB, HYPERPLASIA, Biomarkers, CESSATION

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