Cargando…

Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nurmi, Katariina, Virkanen, Juhani, Rajamäki, Kristiina, Niemi, Katri, Kovanen, Petri T., Eklund, Kari K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823849/
https://www.ncbi.nlm.nih.gov/pubmed/24244322
http://dx.doi.org/10.1371/journal.pone.0078537
_version_ 1782290621286842368
author Nurmi, Katariina
Virkanen, Juhani
Rajamäki, Kristiina
Niemi, Katri
Kovanen, Petri T.
Eklund, Kari K.
author_facet Nurmi, Katariina
Virkanen, Juhani
Rajamäki, Kristiina
Niemi, Katri
Kovanen, Petri T.
Eklund, Kari K.
author_sort Nurmi, Katariina
collection PubMed
description 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-1β 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 pro-IL-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.
format Online
Article
Text
id pubmed-3823849
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38238492013-11-15 Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol Nurmi, Katariina Virkanen, Juhani Rajamäki, Kristiina Niemi, Katri Kovanen, Petri T. Eklund, Kari K. PLoS One Research Article 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-1β 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 pro-IL-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. Public Library of Science 2013-11-11 /pmc/articles/PMC3823849/ /pubmed/24244322 http://dx.doi.org/10.1371/journal.pone.0078537 Text en © 2013 Nurmi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nurmi, Katariina
Virkanen, Juhani
Rajamäki, Kristiina
Niemi, Katri
Kovanen, Petri T.
Eklund, Kari K.
Ethanol 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
title_full Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol
title_fullStr Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol
title_full_unstemmed Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol
title_short Ethanol Inhibits Activation of NLRP3 and AIM2 Inflammasomes in Human Macrophages–A Novel Anti-Inflammatory Action of Alcohol
title_sort ethanol inhibits activation of nlrp3 and aim2 inflammasomes in human macrophages–a novel anti-inflammatory action of alcohol
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823849/
https://www.ncbi.nlm.nih.gov/pubmed/24244322
http://dx.doi.org/10.1371/journal.pone.0078537
work_keys_str_mv AT nurmikatariina ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol
AT virkanenjuhani ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol
AT rajamakikristiina ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol
AT niemikatri ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol
AT kovanenpetrit ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol
AT eklundkarik ethanolinhibitsactivationofnlrp3andaim2inflammasomesinhumanmacrophagesanovelantiinflammatoryactionofalcohol