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.
View: Text | PDF
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

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Dose- and time-dependent effect of IL-13 on MCD. GT335, a mAb that detec...
Dose- and time-dependent effect of IL-13 on MCD. GT335, a mAb that detects glutamylated tubulins, gives the proportion of ciliated cells during MCD in Western blot analysis (14). The indicated numbers represent the days after confluence. (a) Dose-dependent effect of IL-13 on ciliated cell differentiation. The proportion of ciliated cells at day 15 decreases with the dose of the continuously applied cytokine during differentiation. (b) Epithelial cells were continuously treated with IL-13 during proliferation (+/–), differentiation (–/+), or both (+/+), compared with control cultures (–/–). No effect is observed on ciliated cell differentiation when cells are treated with the cytokine during proliferation (+/–). The increased GT335 staining at day 9 (–/+ compared with –/–) is not significant, varying from one experiment to another. Ciliated differentiation is strongly reduced when cells are treated during differentiation (–/+ or +/+). (c) Epithelial cells were either treated for 72 hours (between day 4 and day 7) or continuously treated with IL-13 (10 ng/ml). The maximum effect is observed for a continuous treatment. (d) Epithelial cells were continuously treated with IL-13, IL-4, or IFN-γ (10 ng/ml) during differentiation. IL-13 and IL-4 effects are identical, while IFN-γ does not alter the ciliated cell differentiation process. (e) The IL-4 antagonistic mutant protein (Y124D) antagonizes the IL-13 effect in a dose-dependent manner. The same amount of total protein extracts were deposited per lane (10 μg). Actin or tubulin were revealed as constant protein markers during the kinetics of differentiation.