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

1 Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and 2 Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115 Submitted 22 October 2003 ; accepted in final form 5 Ma...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2004-07, Vol.287 (1), p.L119-L126
Main Authors: Kikuchi, Tadashi, Shively, Jonathan D, Foley, John S, Drazen, Jeffrey M, Tschumperlin, Daniel J
Format: Article
Language:English
Subjects:
Bronchi - cytology
Bronchi - drug effects
Bronchi - metabolism
Cell Differentiation - physiology
Cells, Cultured
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Fluorescent Antibody Technique
Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis
Humans
Interleukin-13 - pharmacology
Interleukin-4 - pharmacology
Phosphorylation
Staining and Labeling
STAT6 Transcription Factor
Trans-Activators - metabolism
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta2
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Summary:1 Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and 2 Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115 Submitted 22 October 2003 ; accepted in final form 5 March 2004 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- 2 (TGF- 2 ) 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- 2 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. bronchial epithelial cells; cell differentiation; interleukin-4/13; granulocyte/macrophage colony-stimulating factor; transforming growth factor- Address for reprint requests and other correspondence: D. J. Tschumperlin, Physiology Program, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115 (E-mail: dtschump{at}hsph.harvard.edu ).
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00365.2003