Journal article

Publication year: 2018

Journal: Toxins

Volume number: 10

Issue number: 2

ISSN: 2072-6651

Open access status: Gold

DOI Link: https://doi.org/10.3390/toxins10020079

Publisher: MDPI

Abstract: 
Pulmonary permeability edema is characterized by reduced alveolar Na+ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na+ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here we examine how listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, impairs the expression and activity of ENaC. To that purpose, we studied how sub-lytic concentrations of LLO affect negative and positive regulators of ENaC expression in the H441 airway epithelial cell line. LLO reduced expression of the crucial ENaC- subunit in H441 cells within 2 h and this was preceded by activation of PKC-, a negative regulator of the channel's expression. At later time points, LLO caused a significant reduction in the phosphorylation of Sgk-1 at residue T256 and of Akt-1 at residue S473, both of which are required for full activation of ENaC. The TNF-derived TIP peptide prevented LLO-mediated PKC- activation and restored phospho-Sgk-1-T256. The TIP peptide also counteracted the observed LLO-induced decrease in amiloride-sensitive Na+ current and ENaC- expression in H441 cells. Intratracheally instilled LLO caused profound pulmonary edema formation in mice, an effect that was prevented by the TIP peptide; thus indicating the therapeutic potential of the peptide for the treatment of pore-forming toxin-associated permeability edema.

Harvard Citation style: Yang, G., Pillich, H., White, R., Czikora, I., Pochic, I., Yue, Q., et al. (2018) Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells, Toxins, 10(2), Article 79. https://doi.org/10.3390/toxins10020079

APA Citation style: Yang, G., Pillich, H., White, R., Czikora, I., Pochic, I., Yue, Q., Hudel, M., Gorshkov, B., Verin, A., Sridhar, S., Isales, C., Eaton, D., Hamacher, J., Chakraborty, T., & Lucas, R. (2018). Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells. Toxins. 10(2), Article 79. https://doi.org/10.3390/toxins10020079