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Alcohol up-regulates TLR2 through a NO/cGMP dependent pathway
Kristina L Bailey1, Joseph H Sisson, Debra J Romberger
1Pulmonary, Critical Care, Sleep & Allergy Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA. kbailey@unmc.edu
Alcoholism, Clinical and Experimental Research
|October 29, 2009
Summary
Heavy alcohol use increases airway inflammation by up-regulating Toll-like receptor 2 (TLR2). This study reveals alcohol increases TLR2 via a nitric oxide (NO)/cGMP/PKG pathway, offering new insights into alcohol-related respiratory issues.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Heavy alcohol consumption is linked to severe bronchitis, likely due to increased airway inflammation.
- Toll-like receptor 2 (TLR2) mediates airway inflammation and is upregulated by alcohol, but the mechanism is unknown.
Purpose of the Study:
- To elucidate the mechanism behind alcohol-mediated upregulation of TLR2 in airway epithelium.
- To investigate the role of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in this process.
Main Methods:
- Human airway epithelial cells (16HBE14o-) were treated with alcohol (100 mM).
- Inhibitors of nitric oxide synthase (NOS) and cGMP-dependent protein kinase (PKG) were used.
- TLR2 expression was quantified using real-time PCR and Western blots.
- Cells were also treated with NO donors and cGMP analogs.
Main Results:
- A NOS inhibitor blocked alcohol-induced TLR2 upregulation, implicating NO.
- An NO donor (SNP) increased TLR2 expression.
- A cGMP antagonist attenuated alcohol's effect, and a cGMP analog increased TLR2, suggesting a NO/cGMP/PKG pathway.
Conclusions:
- Alcohol upregulates TLR2 in airway epithelium via a NO/cGMP/PKG-dependent pathway.
- This pathway is crucial for understanding alcohol's modulation of airway inflammation.
- This study is the first to demonstrate a role for cyclic nucleotides in TLR2 regulation.
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