{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:50:30Z","timestamp":1790650230394,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,11]],"date-time":"2018-02-11T00:00:00Z","timestamp":1518307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERA-NET PathoGenoMics"},{"name":"LISTRESS"},{"DOI":"10.13039\/100001440","name":"ADA Foundation","doi-asserted-by":"publisher","award":["1-16-IBS-196"],"award-info":[{"award-number":["1-16-IBS-196"]}],"id":[{"id":"10.13039\/100001440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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-\u03b1 subunit in H441 cells within 2 h and this was preceded by activation of PKC-\u03b1, a negative regulator of the channel\u2019s 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-\u03b1 activation and restored phospho-Sgk-1-T256. The TIP peptide also counteracted the observed LLO-induced decrease in amiloride-sensitive Na+ current and ENaC-\u03b1 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.<\/jats:p>","DOI":"10.3390\/toxins10020079","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T10:50:38Z","timestamp":1518432638000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Pillich","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus-Liebig University Giessen, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"},{"name":"Department of Biomedical Sciences, Georgia Campus-Philadelphia College of Osteopathic Medicine, Atlanta, GA 30224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-9494","authenticated-orcid":false,"given":"Istvan","family":"Czikora","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Pochic","sequence":"additional","affiliation":[{"name":"Biochemical Pharmacology, University of Konstanz, 78464 Konstanz, Germany"},{"name":"Sandoz Inc., 83607 Holzkirchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory School of Medicine, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Hudel","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus-Liebig University Giessen, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Gorshkov","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Verin","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Sridhar","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Isales","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Georgia, Augusta, GA 30901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Physiology, Emory School of Medicine, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg","family":"Hamacher","sequence":"additional","affiliation":[{"name":"Biochemical Pharmacology, University of Konstanz, 78464 Konstanz, Germany"},{"name":"Department of Pneumology, Lindenhofspital, 3001 Bern, Switzerland"},{"name":"Internal, Pulmonary and Critical Care Medicine, Saarland University, 66424 Homburg\/Saar, Germany"},{"name":"Lungen-und Atmungsstifung, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1452-4759","authenticated-orcid":false,"given":"Trinad","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Justus-Liebig University Giessen, 35392 Gie\u00dfen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Lucas","sequence":"additional","affiliation":[{"name":"Vascular Biology Center, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"},{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Room CB-3213B, Augusta, GA 30912-2500, USA"},{"name":"Department of Medicine, Medical College of Georgia, Augusta, GA 30901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1469-0691.2009.03109.x","article-title":"Listeriosis: A resurgent foodborne infection","volume":"16","author":"Allerberger","year":"2010","journal-title":"Clin. 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