Alcohol Up-Regulates TLR2 Through a NO/cGMP Dependent Pathway

Details

• Personal Author:
  Bailey KL ; Robinson JE ; Romberger DJ ; Sisson JH ; Wyatt TA
• Description:
  Background: Heavy alcohol consumption is associated with severe bronchitis. This is likely related to increased inflammation in the airways of alcohol abusers. Toll-like receptor 2 (TLR2) is an important mediator of inflammation in the airway epithelium. TLR2 initiates an inflammatory cascade in response to gram-positive bacteria. We have previously shown that alcohol up-regulates TLR2 in the airway epithelium. However, the mechanism of alcohol-mediated up-regulation of TLR2 has not been identified. Methods: A human airway epithelial cell line, 16HBE14o-, was exposed to biologically relevant concentrations of alcohol (100 mM) in the presence and absence of Nw-Nitro-L-arginine methyl ester hydrochloride, a nitric oxide (NO) synthase inhibitor; and Rp-8-Br-cGMP-S, an antagonist analogue of cGMP. TLR2 was measured using real-time PCR and Western blots. In addition, 16HBE14o- cells were incubated with sodium nitroprusside (SNP), an NO donor, and 8-Br-cGMP, a cGMP analogue. TLR2 was measured using real-time PCR. Results: Nw-Nitro-L-arginine methyl ester hydrochloride blocked the alcohol-mediated up-regulation of TLR2. This indicates that NO plays a key role in alcohol's up-regulation of TLR2. SNP, a NO donor, up-regulated TLR2. Rp-8-Br-CGMP-S attenuated alcohol's up-regulation of TLR2, suggesting that NO was working through cGMP/PKG. 8-Br-cGMP up-regulated TLR2, also demonstrating the importance of cGMP/PKG. Conclusions: Alcohol up-regulates TLR2 through a NO/cGMP/PKG dependent pathway in the airway epithelium. This is an important observation in the understanding how alcohol modulates airway inflammation. In addition, this is the first time that cyclic nucleotides have been shown to play a role in the regulation of TLR2. [Description provided by NIOSH]
• Subjects:
  Alcoholic Beverages Ethanol Irritants Lung Lung Diseases Nucleotides Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Alcoholism Alcohols Author Keywords: Lung Biological-effects Cyclic Nucleotide Ethanols Humans Inflammation Lung-disease Lung-function Nitric Oxide Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  0145-6008
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  51-56
• Volume:
  34
• Issue:
  1
• NIOSHTIC Number:
  nn:20037336
• Citation:
  Alcohol Clin Exp Res 2010 Jan; 34(1):51-56
• Contact Point Address:
  Kristina L. Bailey, MD, Pulmonary, Critical Care, Sleep & Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5915
• Email:
  kbailey@unmc.edu
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  Alcoholism: Clinical and Experimental Research
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a8a2d46b0b12b22f6b792569a57489457aeb7edb95fd64d72f806e7bed4a0b3636ded14c1448caa8781ee4f8f3a541ec94eafc9b853ba15d112482af55e13dc2
• Download URL:
  https://stacks.cdc.gov/view/cdc/188441/cdc_188441_DS1.pdf
• File Type:
  [PDF - 278.19 KB ]