IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells
Jamila Laoukili, … , Daniel Caput, Frédéric Tournier
Jamila Laoukili, … , Daniel Caput, Frédéric Tournier
Published December 15, 2001
Citation Information: J Clin Invest. 2001;108(12):1817-1824. https://doi.org/10.1172/JCI13557.
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Article

IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells

Abstract

In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration. We have thus investigated the effect of IL-13 on mucociliary differentiation of human nasal epithelial cells in primary culture. We show that IL-13 alters ciliated cell differentiation and increases the proportion of secretory cells. IL-13 downregulates the actin-binding protein ezrin and other cytoskeletal components. IL-13 also impairs lateral cell contacts and interferes with the apical localization of ezrin seen in differentiated ciliated cells. In addition, an IL-4 antagonistic mutant protein (Y124D), which binds to the IL-4 receptor α subunit, a common chain of IL-4 and IL-13 receptors, inhibits IL-13’s effects. IL-13 also decreases ciliary beat frequency in a time- and dose-dependent manner. These results suggest that, in human allergic asthmatic responses, IL-13 affects both ciliated and secretory cell differentiation, leading to airway damage and obstruction.

Authors

Jamila Laoukili, Eric Perret, Tom Willems, Adrian Minty, Eef Parthoens, Odile Houcine, Andre Coste, Mark Jorissen, Francelyne Marano, Daniel Caput, Frédéric Tournier

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Figure 1

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IL-13 modifies the proportion of differentiated phenotypes during MCD. (...
IL-13 modifies the proportion of differentiated phenotypes during MCD. (a) Scheme illustrating the different steps of the primary culture. Cells dissociated from human nasal polyps or turbinates are plated on thick collagen. Basal-like epithelial cells proliferate and form an epithelial monolayer. At confluence (C), collagenase removes epithelial cell sheets that are then rotary shaken to form epithelial spheroids. Epithelial cells then polarize and differentiate into secretory and ciliated cells. (b) Detection of ciliated cells (GT335) and secretory cells (Anti-M1) within epithelial spheroids during MCD in the absence (–IL-13) or in the presence (+IL-13) of the cytokine (by indirect IF). Note the absence of ciliated cells and the high number of secretory cells in the presence of the cytokine. Bar, 10 μm. (c) Quantification of IL-13 effect during MCD (flow cytometry). Cells dissociated from epithelial spheroids were analyzed using GT335 for ciliated cells and anti-M1 for secretory cells during the time course (0–30 days) of MCD. IL-13 (10 ng/ml) decreases the proportion of ciliated cells and largely increases the proportion of secretory cells. Three independent kinetics are shown. Gray symbols, –IL-13; black symbols, +IL-13.