Pneumologie 2015; 69 - P06
DOI: 10.1055/s-0035-1551908

Glucocorticoids and IL-13 modulate the barrier function of NCI-H441 airway epithelia via claudin 8

VE Winkelmann 1, H Schmidt 1, F Kielgast 1, M Frick 1, P Dietl 1, OH Wittekindt 1
  • 1Institute of General Physiology, University of Ulm, Germany

Introduction: In allergic asthma elevated levels of TH2 cytokines, especially IL-13 levels can be observed. Allergic asthma is typically treated with Glucocorticoids (GCs), whose anti-inflammatory properties are the predominant objective of this treatment. Recent studies showed an additional GC effect on the barrier function of the airway epithelium and identified claudin 8 (cldn8) as a major modulator of tight junctions (TJs) properties in lung epithelia.

Herein we addressed whether IL-13 and GCs affects tight junctions in a distal lung epithelial model.

Methods: We used air/liquid cultures of NCI-H441 cells as a well-established cell line based model of the lung epithelium. These epithelia were cultivated in the presence of the GC dexamethasone and IL-13. Expression levels of cldn8 as a major determinant of TJ function in lung as well as the interleukin receptors IL-13Rα1, IL-13Rα2 and IL-4Rα1 were analysed in RT-PCR experiments. Protein quantification and modification of cldn8 was elucidated in western blot experiments. Epithelial barrier function was analysed via measuring the transepithelial electrical resistance (TEER) and in permeability assays.

Results: GCs improved the barrier function of NCI-H441 epithelia and induced a moderate but significant upregulation of IL-13Rα1. Therefore, they may increase sensitivity of these epithelia to IL-13. Indeed, the exposure of NCI-H441 epithelia to IL-13 did not affect overall paracellular permeability, but diminished the Cl- selectivity of TJs. This was accompanied by a downregulation of cldn8 expression and cldn8 phosphorylation.

Discussion: We conclude that IL-13 impairs tight junction properties by modulating cldn8 expression and phosphorylation. That GCs increase IL-13Rα1 expression hints at a more complex role of GCs in treating inflammatory airway diseases like allergic asthma and COPD with respect to epithelial barrier function.

Supported by Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (Az: 32 – 7533.-6 – 10/15/5) to OW