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IL-13 Impairs Tight Junctions in Airway Epithelia

Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Institute of Pathology, Hannover Medical School, Carl-Neuberg-Str. 130625 Hannover, Germany
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;
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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MDPI and ACS Style

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.

AMA Style

Schmidt H, Braubach P, Schilpp C, Lochbaum R, Neuland K, Thompson K, Jonigk D, Frick M, Dietl P, Wittekindt OH. IL-13 Impairs Tight Junctions in Airway Epithelia. International Journal of Molecular Sciences. 2019; 20(13):3222.

Chicago/Turabian Style

Schmidt, Hanna, Peter Braubach, Carolin Schilpp, Robin Lochbaum, Kathrin Neuland, Kristin Thompson, Danny Jonigk, Manfred Frick, Paul Dietl, and Oliver H. Wittekindt 2019. "IL-13 Impairs Tight Junctions in Airway Epithelia" International Journal of Molecular Sciences 20, no. 13: 3222.

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