%0 Journal Article
%T Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages¨CA Novel Anti-Inflammatory Action of Alcohol
%A Katariina Nurmi
%A Juhani Virkanen
%A Kristiina Rajam£¿ki
%A Katri Niemi
%A Petri T. Kovanen
%A Kari K. Eklund
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0078537
%X Objective In the pathogenesis of coronary atherosclerosis, local macrophage-driven inflammation and secretion of proinflammatory cytokines, interleukin-1¦Â (IL-1¦Â) 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-1¦Â. Results Ethanol decreased dose-dependently the production of mature IL-1¦Â 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-1¦Â was decreased in parallel with reduction of caspase-1 activation, demonstrating that ethanol inhibits inflammasome activation instead of synthesis of pro-IL-1¦Â. Acetaldehyde, a highly reactive metabolite of ethanol, had no effect on the ATP-induced IL-1¦Â secretion. Ethanol also attenuated the secretion of IL-1¦Â 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078537