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Updated: Aug 8, 2026
08:37
Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Chronic ethanol-mediated decrease in cAMP primes macrophages to enhanced LPS-inducible NF-kappaB activity and TNF
Leila Gobejishvili1, Shirish Barve, Swati Joshi-Barve
1Dept. of Medicine, Pharmacology and Toxicology, Univ. of Louisville Medical Center, 550 S. Jackson St., ACB 3rd Floor, Louisville, KY 40292, USA. craig.mcclain@louisville.edu
Summary
Chronic ethanol exposure decreases cellular cAMP levels, increasing TNF-alpha production in monocytes. This suggests cAMP-elevating agents may treat alcoholic liver disease (ALD).
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- Alcoholic liver disease (ALD) pathogenesis involves increased TNF-alpha.
- Monocytes from alcoholic patients exhibit enhanced NF-kappaB activation and TNF-alpha production.
- Cellular cAMP regulates TNF-alpha expression, with elevated cAMP suppressing production.
Purpose of the Study:
- To investigate the effects of chronic ethanol exposure on cAMP levels and TNF expression in monocytes and Kupffer cells.
- To elucidate the role of cAMP in ethanol-induced TNF-alpha production in ALD.
Main Methods:
- In vitro and in vivo (rat model) experiments.
- Analysis of cellular cAMP levels in monocytes and Kupffer cells.
- Assessment of TNF-alpha production and NF-kappaB activation.
- Evaluation of TNF mRNA expression and stability.
- Intervention with dibutyryl cAMP to modulate cAMP levels.
Main Results:
- Chronic ethanol exposure significantly decreased cellular cAMP levels in monocytes.
- Ethanol increased LPS-inducible TNF-alpha production by affecting NF-kappaB activation and TNF mRNA induction.
- cAMP enhancement abrogated LPS-mediated TNF-alpha expression in ethanol-treated cells.
- cAMP decreased NF-kappaB transcriptional activity but not its activation.
Conclusions:
- Ethanol synergizes with LPS to upregulate TNF gene expression and TNF overproduction by reducing cellular cAMP levels in monocytes/macrophages.
- cAMP-elevating agents show therapeutic potential for attenuating ALD progression.
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