Search resultsEthanol inhibits activation of NLRP3 and AIM2 inflammasomes in human macrophages - A novel anti-inflammatory action of alcohol
Title
Ethanol inhibits activation of NLRP3 and AIM2 inflammasomes in human macrophages - A novel anti-inflammatory action of alcohol
Publication type
Journal Article
Year of Publication
2013
Authors
Journal
PLoS ONE
Volume
8
Issue
11
Date published
2013
ISBN
19326203 (ISSN)
Keywords
acetaldehyde, AIM2, alcohol, alcohol consumption, Alcohol Drinking, Anti-Inflammatory Agents, Non-Steroidal, antiinflammatory activity, article, Carrier Proteins, caspase 8, cathepsin B, cell death, Cell Line, Tumor, Central Nervous System Depressants, Cholesterol, Coronary Disease, cryopyrin, crystallization, cytokine production, cytokine release, enzyme activation, enzyme inhibition, enzyme linked immunosorbent assay, Ethanol, human, Humans, inflammasome, Inflammasomes, interleukin 18, interleukin 1beta, interleukin 1beta converting enzyme, Interleukin-1beta, ischemic heart disease, Lipopolysaccharides, lysosome, macrophage, Macrophages, Nuclear Proteins, oligomerization, quantitative analysis, real time polymerase chain reaction, serum amyloid A, toll like receptor 2, toll like receptor 4, unclassified drug, Western blotting
Abstract
Objective: In the pathogenesis of coronary atherosclerosis, local macrophage-driven inflammation and secretion of proinflammatory cytokines, interleukin-1β (IL-1β) in particular, are recognized as key factors. Moderate alcohol consumption is associated with a reduced risk of coronary artery disease mortality. Here we examined in cultured human macrophages whether ethanol modulates the intracellular processes involved in the secretion of IL-1β. Results: Ethanol decreased dose-dependently the production of mature IL-1b induced by activators of the NLRP3 inflammasome, i.e. ATP, cholesterol crystals, serum amyloid A and nigericin. Ethanol had no significant effect on the expression of NLRP3 or IL1B mRNA in LPS-primed macrophages. Moreover, secretion of IL-1β was decreased in parallel with reduction of caspase-1 activation, demonstrating that ethanol inhibits inflammasome activation instead of synthesis of proIL-1β. Acetaldehyde, a highly reactive metabolite of ethanol, had no effect on the ATP-induced IL-1β secretion. Ethanol also attenuated the secretion of IL-1β triggered by synthetic double-stranded DNA, an activator of the AIM2 inflammasome. Ethanol conferred the inhibitory functions by attenuating the disruption of lysosomal integrity and ensuing leakage of the lysosomal protease cathepsin B and by reducing oligomerization of ASC. Conclusion: Ethanol-induced inhibition of the NLRP3 inflammasome activation in macrophages may represent a biological pathway underlying the protective effect of moderate alcohol consumption on coronary heart disease.