Alcohol Use Disorders are Associated with a Unique Impact on Airways Epithelial Cell Gene Expression

Details

• Journal Article:
  Alcohol Clin Exp Res
• Personal Author:
  Bailey, Kristina L. ; Smith, Harry ; Mathai, Susan K. ; Huber, Jonathan ; Yacoub, Mark ; Yang, Ivana V. ; Wyatt, Todd A. ; Kechris, Katerina ; Burnham, Ellen L.
• Description:
  Background.
  
  Alcohol use disorders (AUDs) and cigarette smoking both increase risk for development of community-acquired pneumonia (CAP), likely through adverse effects on proximal airway mucociliary clearance and pathogen recognition. Smoking-related alterations on airways gene expression are well-described, but little is known about the impact of AUDs. We measured gene expression in human airways epithelial cells (AECs), hypothesizing that AUDs would be associated with novel differences in gene expression that could alter risk for CAP.
  
  Methods.
  
  Bronchoscopy with airway brushings were performed in participants with AUDs and controls to obtain AECs. An Alcohol Use Disorders Identification Test was used to define AUD. RNA was extracted from AECs, and mRNA expression data were collected on an Agilent micro-array. Differential expression analyses were performed on the filtered and normalized data with correction for multiple testing. Enrichment analyses were performed using clusterProfiler.
  
  Results.
  
  Expression data from 19 control and 18 AUD participants were evaluated. After adjustment for smoking, AUDs were associated with significant differential expression of 520 AEC genes, including genes for ribosomal proteins and genes involved in protein folding. Enrichment analyses indicated significant differential expression of 24 pathways in AUDs, including those implicated in protein targeting to membrane and viral gene expression. Smoking-associated AEC gene expression differences mirrored previous reports, but differed from those associated with AUDs.
  
  Conclusions.
  
  AUDs have a distinct impact on AEC gene expression that may influence proximal airway function independent of smoking. Alcohol-associated alterations may influence risk for CAP through modifying key mechanisms important in protecting proximal airways integrity.
  
  
• Subjects:
  Alcoholism Bronchoscopy Case-Control Studies Cigarette Smoking Community-Acquired Infections Epithelial Cells Gene Expression Pneumonia Respiratory Mucosa Risk Factors RNA, Messenger Transcriptome

  More +
• Keywords:
  Alcohol; Alcoholism; Gene Expression; Cigarette Smoking; Lung Disease; Respiratory Function; Pneumonia; Smoke Inhalation; Genetic Factors; Author Keywords: Alcoholism; Smoking; Micro-array; Community-Acquired Pneumonia; Bronchoscopy
• Source:
  Alcohol Clin Exp Res. 44(8):1571-1584
• Pubmed ID:
  32524622
• Pubmed Central ID:
  PMC7484391
• Document Type:
  Text
• Funding:
  IK6 BX003781/BX/BLRD VAUnited States/ ; UL1TR001082/TR/NCATS NIH HHSUnited States/ ; K23 HL136785/HL/NHLBI NIH HHSUnited States/ ; R21 HL121572/HL/NHLBI NIH HHSUnited States/ ; R21HL121572/HL/NHLBI NIH HHSUnited States/ ; R24 AA019661/AA/NIAAA NIH HHSUnited States/ ; I01 BX003635/BX/BLRD VAUnited States/ ; K23HL136785/HL/NHLBI NIH HHSUnited States/ ; UL1 TR001082/TR/NCATS NIH HHSUnited States/ ; R01 AA021131/AA/NIAAA NIH HHSUnited States/ ; U54 OH010162/OH/NIOSH CDC HHSUnited States/
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Nebraska ; OSHA Region 6 ; OSHA Region 7 ; OSHA Region 8 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  26 pdf pages
• Volume:
  44
• Issue:
  8
• NIOSHTIC Number:
  nn:20065137
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b7fb17eba6519e34fe8b92a2c1b5fa623af6467e54d9e4b4473ff57a6ac4e8960015a22e9f2e36c68dc2f0ee7bd92c1161a392113c02d75d43e5b89c513cc4d6
• Download URL:
  https://stacks.cdc.gov/view/cdc/113140/cdc_113140_DS1.pdf
• File Type:
  [PDF - 778.74 KB ]