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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IL-13 effect on partially differentiated epithelial spheroids: IL-13 inh...
IL-13 effect on partially differentiated epithelial spheroids: IL-13 inhibits further ciliogenesis, increases the proportion of MUC5AC-positive cells, and decreases ciliary beat frequency. (a) Partially differentiated (ciliated) epithelial spheroids (18 days after confluence) were continuously treated with IL-13 for 11 days and processed for double IF analysis (day 29). The proportion of ciliated cells remained lower than in control conditions after IL-13 treatment (single staining, GT335: compare –IL-13 and +IL-13). Numerous MUC5AC-positive cells (Anti-M1) were observed in the IL-13–treated conditions compared with control conditions. Accordingly, the proportion of epithelial cells with ezrin located within the apical membrane domain was lower in the presence of the cytokine. Note that ezrin staining is absent in MUC5AC-positive cells (+IL-13, Anti-M1/anti-ezrin). Bar, 10 μm. (b) The effect of IL-13 on CBF was determined on partially differentiated spheroids (21 days in suspension after confluence). The CBF was measured after 1, 3, and 6 days. CBF does not change significantly after 1 and 3 days of continuous treatment with IL-13. A significant concentration-dependent downregulation of the CBF values is observed after 6 days of continuous stimulation (0, 1, 10, 100 ng/ml of IL-13). The values are expressed as mean ± SD. The Student t test was used to compare IL-13–stimulated cells and controls at the same incubation time. A value of P < 0.05 was accepted as statistically significant (* P < 0.02; **P < 0.01; ***P < 0.0001).