Differentiation-dependent responsiveness of bronchial epithelial cells to IL-4/13 stimulation

Tadashi Kikuchi, Jonathan D. Shively, John S. Foley, Jeffrey M. Drazen, Daniel J. Tschumperlin

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The Th2 cytokines interleukin (IL)-4 and IL-13 are thought to play critical roles in the airway inflammation and hyperresposiveness that characterize asthma. Recent evidence indicates that IL-13 can mediate these effects by acting directly on airway epithelial cells. Here we evaluated early [signal transducer and activator of transcription (STAT)6 phosphorylation] and delayed [granulocyte/macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β2 (TGF-β2) secretion] responses of airway epithelial cells to IL-4 and IL-13 stimulation and the dependence of these responses on the culture technique employed. As expected, normal human bronchial epithelial cells grown on microporous inserts at an air-liquid interface (ALI) expressed a well-differentiated mucociliary phenotype; in contrast, cells grown on plastic in submerged cultures were poorly differentiated. When stimulated with IL-4 or IL-13, the magnitude and duration of STAT6 phosphorylation under the differing culture conditions were statistically indistinguishable. In contrast, cytokine secretion responses to IL-4 and IL-13 were highly dependent on the culture technique; cells cultured on plastic exhibited significant concentration-dependent increases in GM-CSF and TGF-β2 secretion, whereas cells grown at ALI showed no statistically significant response. These results demonstrate that the coupling between early signal transduction responses to IL-4 and IL-13 and downstream functions such as cytokine secretion may be critically dependent on the cell culture technique employed and the resulting differentiation status of bronchial epithelial cells.

Original languageEnglish (US)
Pages (from-to)L119-L126
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number1 31-1
DOIs
StatePublished - Jul 1 2004

Keywords

  • Bronchial epithelial cells
  • Cell differentiation
  • Granulocyte/macrophage colony-stimulating factor
  • Interleukin-4/13
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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