(Chest. 2003;123:373S-374S.)
© 2003
American College of Chest Physicians
Interleukin-13 Alters Mucociliary Differentiation of Human Nasal Epithelial Cells*
Marie Skowron, PhD(c);
Eric Perret, PhD;
Francelyne Marano, PhD;
Daniel Caput, PhD and
Frédéric Tournier, PhD
* From the Laboratoire de Cytophysiologie et Toxicologie Cellulaire (Drs. Skowron, Tournier, and Marano), Université Paris, Paris, France; and Sanofi-Synthelabo Recherche (Drs. Perret and Caput), Labège, France.
Correspondence to: Frédéric Tournier, PhD, Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Case 7073, Tour 53-54, 3ème Étage, 2, Place Jussieu, 75251 Paris Cedex 05, France; e-mail: f-tournier{at}paris7.jussieu.fr
Lesions of the airway epithelium are frequently observed in asthma patients. Therefore, inflammatory mediators such as chemokines or cytokines may influence airway remodeling. Among these cytokines, interleukin (IL)-13 recently has emerged as a pivotal molecule with which to promote airway hyperresponsiveness.1
We have investigated the effect of IL-13 on the mucociliary differentiation of human nasal epithelial cells in primary culture. IL-13 alters ciliated cell differentiation and, in parallel, largely increases the proportion of secretory cells in a dose-dependent and time-dependent manner, and impairs lateral cell contacts. Treatment with IL-13 and increasing amounts of an IL-4 mutant (Y124D), which is a selective antagonist of the IL-4/IL-13 shared receptor, abolishes the effects of IL-13.2
Using differential screening of treated and nontreated epithelial cells during differentiation, we showed that transforming growth factor-ß1 gene expression is increased in the presence of the cytokine, reinforcing the idea that IL-13 could induce tissue fibrosis by selectively activating transforming growth factor-ß1, as was recently shown in mice.3
Because multiple IL-13 effects contribute to the asthma phenotype, inhibiting the cytokine or its receptors in vivo may be relevant in patients with chronic lung diseases such as asthma.
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References
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- Corry, DB (1999) IL-13 in allergy: home at last. Curr Opin Immunol 11,610-614[CrossRef][Medline]
- Laoukili, J, Perret, E, Willems, T, et al IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells. J Clin Invest 2001;108,1817-1824[CrossRef][ISI][Medline]
- Lee, CG, Homer, RJ, Zhu, Z, et al Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor ß1. J Exp Med 2001;194,809-821[Abstract/Free Full Text]