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Open AccessArticle

IL-13 Impairs Tight Junctions in Airway Epithelia

1
Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
2
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 130625 Hannover, Germany
3
German Center of Lung Research (DZL), Partnersite BREATH, 306245 Hannover, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3222; https://doi.org/10.3390/ijms20133222
Received: 11 June 2019 / Accepted: 27 June 2019 / Published: 30 June 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Interleukin-13 (IL-13) drives symptoms in asthma with high levels of T-helper type 2 cells (Th2-cells). Since tight junctions (TJ) constitute the epithelial diffusion barrier, we investigated the effect of IL-13 on TJ in human tracheal epithelial cells. We observed that IL-13 increases paracellular permeability, changes claudin expression pattern and induces intracellular aggregation of the TJ proteins zonlua occludens protein 1, as well as claudins. Furthermore, IL-13 treatment increases expression of ubiquitin conjugating E2 enzyme UBE2Z. Co-localization and proximity ligation assays further showed that ubiquitin and the proteasomal marker PSMA5 co-localize with TJ proteins in IL-13 treated cells, showing that TJ proteins are ubiquitinated following IL-13 exposure. UBE2Z upregulation occurs within the first day after IL-13 exposure. Proteasomal aggregation of ubiquitinated TJ proteins starts three days after IL-13 exposure and transepithelial electrical resistance (TEER) decrease follows the time course of TJ-protein aggregation. Inhibition of JAK/STAT signaling abolishes IL-13 induced effects. Our data suggest that that IL-13 induces ubiquitination and proteasomal aggregation of TJ proteins via JAK/STAT dependent expression of UBE2Z, resulting in opening of TJs. This may contribute to barrier disturbances in pulmonary epithelia and lung damage of patients with inflammatory lung diseases. View Full-Text
Keywords: lung; epithelia; interleukin 13; tight junction; UBE2Z; ubiquitin lung; epithelia; interleukin 13; tight junction; UBE2Z; ubiquitin
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Schmidt, H.; Braubach, P.; Schilpp, C.; Lochbaum, R.; Neuland, K.; Thompson, K.; Jonigk, D.; Frick, M.; Dietl, P.; Wittekindt, O.H. IL-13 Impairs Tight Junctions in Airway Epithelia. Int. J. Mol. Sci. 2019, 20, 3222.

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