Alcohol potentiates RSV-mediated injury to ciliated airway epithelium.

Autor: Wyatt TA; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, United States; University of Nebraska Medical Center, Department of Environmental, Agricultural, & Occupational Health, Omaha, NE, 68198-5910, United States. Electronic address: twyatt@unmc.edu., Bailey KL; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States; Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, United States., Simet SM; University of Nebraska Medical Center, Department of Genetics, Cell Biology & Anatomy, Omaha, NE, 68198-6395, United States., Warren KJ; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States., Sweeter JM; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States., DeVasure JM; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States., Pavlik JA; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States., Sisson JH; University of Nebraska Medical Center, Pulmonary, Critical Care, Sleep & Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, United States.
Jazyk: angličtina
Zdroj: Alcohol (Fayetteville, N.Y.) [Alcohol] 2019 Nov; Vol. 80, pp. 17-24. Date of Electronic Publication: 2018 Jul 26.
DOI: 10.1016/j.alcohol.2018.07.010
Abstrakt: Alcohol impairs resolution of respiratory viral infections. Numerous immune response pathways are altered in response to alcohol misuse, including alcohol-induced ciliary dysfunction in the lung. We hypothesized that mucociliary clearance-mediated innate immunity to respiratory syncytial virus (RSV) would be compromised by alcohol exposure. Cilia were assayed using Sisson-Ammons Video Analysis by quantitating the average number of motile points in multiple whole field measurements of mouse tracheal epithelial cells grown on an air-liquid interface. Pretreatment with ethanol alone (100 mM for 24 hours) had no effect on the number of motile cilia. A single dose (TCID 50 1 × 10 5 ) of RSV resulted in a significant (p < 0.05) decrease in motile cilia after 2 days. Ethanol pretreatment significantly (p < 0.05) potentiated RSV-induced cilia loss by 2 days. Combined RSV and ethanol treatment led to a sustained activation-induced auto-downregulation of PKC epsilon (PKCε). Ethanol-induced enhancement of ciliated cell detachment was confirmed by dynein ELISA and LDH activity from the supernates. RSV-induced cilia loss was evident until 7 days, when RSV-only infected cells demonstrated no significant cilia loss vs. control cells. However, cells pretreated with ethanol showed significant cilia loss until 10 days post-RSV infection. To address the functional significance of ethanol-enhanced cilia detachment, mice fed alcohol ad libitum (20% for 12 weeks) were infected once with RSV, and clearance was measured by plaque-forming assay from lung homogenates for up to 7 days. After 3 days, RSV plaque formation was no longer detected from the lungs of control mice, while significant (p < 0.01) RSV plaque-forming units were detected at 7 days in alcohol-fed mice. Alcohol-fed mice demonstrated enhanced cilia loss and delayed cilia recovery from tracheal measurements in wild-type C57BL/6 mice, but not PKCε KO mice. These data suggest that alcohol worsens RSV-mediated injury to ciliated epithelium in a PKCε-dependent manner.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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