TLR2 and TLR4 expression and inflammatory cytokines are altered in the airway epithelium of those with alcohol use disorders

Details

• Alternative Title:
  Alcohol Clin Exp Res
• Personal Author:
  Bailey, KL ; Romberger, DJ ; Katafiasz, DM ; Heires, AJ ; Sisson, JH ; Wyatt, TA ; Burnham, EL
• Description:
  Background
  
  The lung has a highly regulated system of innate immunity to protect itself from inhaled microbes and toxins. The first line of defense is mucociliary clearance, but if invaders overcome this, inflammatory pathways are activated. Toll-like receptors (TLRs) are expressed on the airway epithelium. Their signaling initiates the inflammatory cascade and leads to production of inflammatory cytokines such as IL-6 and IL-8. We hypothesized that airway epithelial insults, including heavy alcohol intake or smoking, would alter the expression of TLRs on the airway epithelium
  
  Methods
  
  Bronchoscopy with bronchoalveolar lavage and brushings of the airway epithelium was performed in otherwise healthy subjects who had normal chest radiographs and spirometry. A history of alcohol use disorders (AUDs) was ascertained using the Alcohol Use Disorders Identification Test (AUDIT), and a history of cigarette smoking was also obtained. Age, gender and nutritional status in all groups were similar. We used real-time PCR to quantitate TLR1-TLR9 and enzyme-linked immune assay (ELISA) to measure TNFα, IL-6 and IL-8.
  
  Results
  
  Airway brushings were obtained from 26 non-smoking/non-AUD subjects; 28 smoking/non-AUD subjects; 36 smoking/AUD subjects; and 17 non-smoking/AUD subjects. We found that TLR2 is upregulated in AUD subjects, compared to non-smoking/non-AUD subjects, and correlated with their AUDIT scores. We also measured a decrease in TLR4 expression in AUD subjects that correlated with AUDIT score. IL-6 and IL-8 were also increased in bronchial washings from AUD subjects.
  
  Conclusions
  
  We have previously demonstrated in normal human bronchial epithelial (NHBE) cells that in vitro alcohol exposure upregulates TLR2 though a NO/cGMP/PKG dependent pathway, resulting in upregulation of inflammatory cytokine production after gram-positive bacterial product stimulation. Our current translational study confirms that TLR2 is also upregulated in humans with AUDs.
  
  
• Subjects:
  Adult Airway Epithelium Alcohol-Related Disorders Article Cells, Cultured Cohort Studies Cytokines Female Gene Expression Regulation Human Humans Inflammation Mediators Male Middle Aged Respiratory Mucosa Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-like Receptors

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• Source:
  Alcohol Clin Exp Res. 39(9):1691-1697
• Pubmed ID:
  26208141
• Pubmed Central ID:
  PMC4843766
• Document Type:
  Journal Article
• Funding:
  R01AA008769/AA/NIAAA NIH HHSUnited States/ ; R01 AA008769/AA/NIAAA NIH HHSUnited States/ ; K08AA019503/AA/NIAAA NIH HHSUnited States/ ; R24 AA019661/AA/NIAAA NIH HHSUnited States/ ; UL1 TR001082/TR/NCATS NIH HHSUnited States/ ; U54 OH010162/OH/NIOSH CDC HHSUnited States/ ; K08 AA019503/AA/NIAAA NIH HHSUnited States/ ; R24AA019661/AA/NIAAA NIH HHSUnited States/
• Volume:
  39
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:3842de90c9c700ca2ab617e7f85021d2fb0fef1ba6121090e6e7d42a5ebe3e2d
• Download URL:
  https://stacks.cdc.gov/view/cdc/113134/cdc_113134_DS1.pdf
• File Type:
  [PDF - 1.49 MB ]