IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells.
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 alpha 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.
Laoukili
J
J
Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris 7, Paris, France.
Perret
E
E
Willems
T
T
Minty
A
A
Parthoens
E
E
Houcine
O
O
Coste
A
A
Jorissen
M
M
Marano
F
F
Caput
D
D
Tournier
F
F
D001249:Asthma / Q000209:etiology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000502:physiology; D055262:Mucin-2; D009077:Mucins / Q000235:genetics; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects; D010750:Phosphoproteins / Q000032:analysis; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D018793:Interleukin-13; D015847:Interleukin-4; D055262:Mucin-2; D009077:Mucins; D010750:Phosphoproteins; D000099149:Ezrin; C524625:MUC2 protein, human