Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages

Autores
Caceres, Lourdes Catalina; Abogunloko, Tijani; Malchow, Sara; Ehret, Fabienne; Merz, Julian; Li, Xiaowei; Sol Mitre, Lucia; Magnani, Natalia Daniela; Tasat, Deborah Ruth; Mwinyella, Timothy; Spiga, Lisa; Suchanek, Dymphie; Fischer, Larissa; Gorka, Oliver; Colin Gissler, Mark; Hilgendorf, Ingo; Stachon, Peter; Rog Zielinska, Eva; Groß, Olaf; Westermann, Dirk; Evelson, Pablo Andrés; Wolf, Dennis; Marchini, Timoteo Oscar
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Exposure to air pollution fine particulate matter (PM2.5) aggravates respiratory and cardiovascular diseases. It has been proposed that PM2.5 uptake by alveolar macrophages promotes local inflammation that ignites a systemic response, but precise underlying mechanisms remain unclear. Here, we demonstrate that PM2.5 phagocytosis leads to NLRP3 inflammasome activation and subsequent release of the pro-inflammatory master cytokine IL-1β. Inflammasome priming and assembly was time- and dose-dependent in inflammasome-reporter THP-1-ASC-GFP cells, and consistent across PM2.5 samples of variable chemical composition. While inflammasome activation was promoted by different PM2.5 surrogates, significant IL-1β release could only be observed after stimulation with transition-metal rich Residual Oil Fly Ash (ROFA) particles. This effect was confirmed in primary human monocyte-derived macrophages and murine bone marrow-derived macrophages (BMDMs), and by confocal imaging of inflammasome-reporter ASC-Citrine BMDMs. IL-1β release by ROFA was dependent on the NLRP3 inflammasome, as indicated by lack of IL-1β production in ROFA-exposed NLRP3-deficient (Nlrp3−/−) BMDMs, and by specific NLRP3 inhibition with the pharmacological compound MCC950. In addition, while ROFA promoted the upregulation of pro-inflammatory gene expression and cytokines release, MCC950 reduced TNF-α, IL-6, and CCL2 production. Furthermore, inhibition of TNF-α with a neutralizing antibody decreased IL-1β release in ROFA-exposed BMDMs. Using electron tomography, ROFA particles were observed inside intracellular vesicles and mitochondria, which showed signs of ultrastructural damage. Mechanistically, we identified lysosomal rupture, K+ efflux, and impaired mitochondrial function as important prerequisites for ROFA-mediated IL-1β release. Interestingly, specific inhibition of superoxide anion production (O2•-) from mitochondrial respiratory Complex I, but not III, blunted IL-1β release in ROFA-exposed BMDMs. Our findings unravel the mechanism by which PM2.5 promotes IL-1β release in macrophages and provide a novel link between innate immune response and exposure to air pollution PM2.5.
Fil: Caceres, Lourdes Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Abogunloko, Tijani. Albert Ludwigs University of Freiburg; Alemania
Fil: Malchow, Sara. Albert Ludwigs University of Freiburg; Alemania
Fil: Ehret, Fabienne. Albert Ludwigs University of Freiburg; Alemania
Fil: Merz, Julian. Albert Ludwigs University of Freiburg; Alemania
Fil: Li, Xiaowei. Albert Ludwigs University of Freiburg; Alemania
Fil: Sol Mitre, Lucia. Albert Ludwigs University of Freiburg; Alemania
Fil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Tasat, Deborah Ruth. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina
Fil: Mwinyella, Timothy. Albert Ludwigs University of Freiburg; Alemania
Fil: Spiga, Lisa. Albert Ludwigs University of Freiburg; Alemania
Fil: Suchanek, Dymphie. Albert Ludwigs University of Freiburg; Alemania
Fil: Fischer, Larissa. Albert Ludwigs University of Freiburg; Alemania
Fil: Gorka, Oliver. Albert Ludwigs University of Freiburg; Alemania
Fil: Colin Gissler, Mark. Albert Ludwigs University of Freiburg; Alemania
Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania
Fil: Stachon, Peter. Albert Ludwigs University of Freiburg; Alemania
Fil: Rog Zielinska, Eva. Albert Ludwigs University of Freiburg; Alemania
Fil: Groß, Olaf. Albert Ludwigs University of Freiburg; Alemania
Fil: Westermann, Dirk. Albert Ludwigs University of Freiburg; Alemania
Fil: Evelson, Pablo Andrés. Albert Ludwigs University of Freiburg; Alemania
Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania
Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Materia
INFLAMMATION
K+ EFFLUX
LYSOSOMAL DISRUPTION
MACROPHAGES
MITOCHONDRIA
PARTICULATE MATTER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227977
Acceder
id CONICETDig_386f5589f91ea6788c50fc106e4476d1
oai_identifier_str oai:ri.conicet.gov.ar:11336/227977
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophagesCaceres, Lourdes CatalinaAbogunloko, TijaniMalchow, SaraEhret, FabienneMerz, JulianLi, XiaoweiSol Mitre, LuciaMagnani, Natalia DanielaTasat, Deborah RuthMwinyella, TimothySpiga, LisaSuchanek, DymphieFischer, LarissaGorka, OliverColin Gissler, MarkHilgendorf, IngoStachon, PeterRog Zielinska, EvaGroß, OlafWestermann, DirkEvelson, Pablo AndrésWolf, DennisMarchini, Timoteo OscarINFLAMMATIONK+ EFFLUXLYSOSOMAL DISRUPTIONMACROPHAGESMITOCHONDRIAPARTICULATE MATTERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Exposure to air pollution fine particulate matter (PM2.5) aggravates respiratory and cardiovascular diseases. It has been proposed that PM2.5 uptake by alveolar macrophages promotes local inflammation that ignites a systemic response, but precise underlying mechanisms remain unclear. Here, we demonstrate that PM2.5 phagocytosis leads to NLRP3 inflammasome activation and subsequent release of the pro-inflammatory master cytokine IL-1β. Inflammasome priming and assembly was time- and dose-dependent in inflammasome-reporter THP-1-ASC-GFP cells, and consistent across PM2.5 samples of variable chemical composition. While inflammasome activation was promoted by different PM2.5 surrogates, significant IL-1β release could only be observed after stimulation with transition-metal rich Residual Oil Fly Ash (ROFA) particles. This effect was confirmed in primary human monocyte-derived macrophages and murine bone marrow-derived macrophages (BMDMs), and by confocal imaging of inflammasome-reporter ASC-Citrine BMDMs. IL-1β release by ROFA was dependent on the NLRP3 inflammasome, as indicated by lack of IL-1β production in ROFA-exposed NLRP3-deficient (Nlrp3−/−) BMDMs, and by specific NLRP3 inhibition with the pharmacological compound MCC950. In addition, while ROFA promoted the upregulation of pro-inflammatory gene expression and cytokines release, MCC950 reduced TNF-α, IL-6, and CCL2 production. Furthermore, inhibition of TNF-α with a neutralizing antibody decreased IL-1β release in ROFA-exposed BMDMs. Using electron tomography, ROFA particles were observed inside intracellular vesicles and mitochondria, which showed signs of ultrastructural damage. Mechanistically, we identified lysosomal rupture, K+ efflux, and impaired mitochondrial function as important prerequisites for ROFA-mediated IL-1β release. Interestingly, specific inhibition of superoxide anion production (O2•-) from mitochondrial respiratory Complex I, but not III, blunted IL-1β release in ROFA-exposed BMDMs. Our findings unravel the mechanism by which PM2.5 promotes IL-1β release in macrophages and provide a novel link between innate immune response and exposure to air pollution PM2.5.Fil: Caceres, Lourdes Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Abogunloko, Tijani. Albert Ludwigs University of Freiburg; AlemaniaFil: Malchow, Sara. Albert Ludwigs University of Freiburg; AlemaniaFil: Ehret, Fabienne. Albert Ludwigs University of Freiburg; AlemaniaFil: Merz, Julian. Albert Ludwigs University of Freiburg; AlemaniaFil: Li, Xiaowei. Albert Ludwigs University of Freiburg; AlemaniaFil: Sol Mitre, Lucia. Albert Ludwigs University of Freiburg; AlemaniaFil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Tasat, Deborah Ruth. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; ArgentinaFil: Mwinyella, Timothy. Albert Ludwigs University of Freiburg; AlemaniaFil: Spiga, Lisa. Albert Ludwigs University of Freiburg; AlemaniaFil: Suchanek, Dymphie. Albert Ludwigs University of Freiburg; AlemaniaFil: Fischer, Larissa. Albert Ludwigs University of Freiburg; AlemaniaFil: Gorka, Oliver. Albert Ludwigs University of Freiburg; AlemaniaFil: Colin Gissler, Mark. Albert Ludwigs University of Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; AlemaniaFil: Stachon, Peter. Albert Ludwigs University of Freiburg; AlemaniaFil: Rog Zielinska, Eva. Albert Ludwigs University of Freiburg; AlemaniaFil: Groß, Olaf. Albert Ludwigs University of Freiburg; AlemaniaFil: Westermann, Dirk. Albert Ludwigs University of Freiburg; AlemaniaFil: Evelson, Pablo Andrés. Albert Ludwigs University of Freiburg; AlemaniaFil: Wolf, Dennis. Albert Ludwigs University of Freiburg; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaElsevier2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227977Caceres, Lourdes Catalina; Abogunloko, Tijani; Malchow, Sara; Ehret, Fabienne; Merz, Julian; et al.; Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages; Elsevier; Environmental Pollution; 341; 11-2023; 122997-1230090269-7491CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0269749123019991info:eu-repo/semantics/altIdentifier/doi/10.1016/j.envpol.2023.122997info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:11:48Zoai:ri.conicet.gov.ar:11336/227977instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:11:48.821CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
title Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
spellingShingle Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
Caceres, Lourdes Catalina
INFLAMMATION
K+ EFFLUX
LYSOSOMAL DISRUPTION
MACROPHAGES
MITOCHONDRIA
PARTICULATE MATTER
title_short Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
title_full Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
title_fullStr Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
title_full_unstemmed Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
title_sort Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages
dc.creator.none.fl_str_mv Caceres, Lourdes Catalina
Abogunloko, Tijani
Malchow, Sara
Ehret, Fabienne
Merz, Julian
Li, Xiaowei
Sol Mitre, Lucia
Magnani, Natalia Daniela
Tasat, Deborah Ruth
Mwinyella, Timothy
Spiga, Lisa
Suchanek, Dymphie
Fischer, Larissa
Gorka, Oliver
Colin Gissler, Mark
Hilgendorf, Ingo
Stachon, Peter
Rog Zielinska, Eva
Groß, Olaf
Westermann, Dirk
Evelson, Pablo Andrés
Wolf, Dennis
Marchini, Timoteo Oscar
author Caceres, Lourdes Catalina
author_facet Caceres, Lourdes Catalina
Abogunloko, Tijani
Malchow, Sara
Ehret, Fabienne
Merz, Julian
Li, Xiaowei
Sol Mitre, Lucia
Magnani, Natalia Daniela
Tasat, Deborah Ruth
Mwinyella, Timothy
Spiga, Lisa
Suchanek, Dymphie
Fischer, Larissa
Gorka, Oliver
Colin Gissler, Mark
Hilgendorf, Ingo
Stachon, Peter
Rog Zielinska, Eva
Groß, Olaf
Westermann, Dirk
Evelson, Pablo Andrés
Wolf, Dennis
Marchini, Timoteo Oscar
author_role author
author2 Abogunloko, Tijani
Malchow, Sara
Ehret, Fabienne
Merz, Julian
Li, Xiaowei
Sol Mitre, Lucia
Magnani, Natalia Daniela
Tasat, Deborah Ruth
Mwinyella, Timothy
Spiga, Lisa
Suchanek, Dymphie
Fischer, Larissa
Gorka, Oliver
Colin Gissler, Mark
Hilgendorf, Ingo
Stachon, Peter
Rog Zielinska, Eva
Groß, Olaf
Westermann, Dirk
Evelson, Pablo Andrés
Wolf, Dennis
Marchini, Timoteo Oscar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv INFLAMMATION
K+ EFFLUX
LYSOSOMAL DISRUPTION
MACROPHAGES
MITOCHONDRIA
PARTICULATE MATTER
topic INFLAMMATION
K+ EFFLUX
LYSOSOMAL DISRUPTION
MACROPHAGES
MITOCHONDRIA
PARTICULATE MATTER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Exposure to air pollution fine particulate matter (PM2.5) aggravates respiratory and cardiovascular diseases. It has been proposed that PM2.5 uptake by alveolar macrophages promotes local inflammation that ignites a systemic response, but precise underlying mechanisms remain unclear. Here, we demonstrate that PM2.5 phagocytosis leads to NLRP3 inflammasome activation and subsequent release of the pro-inflammatory master cytokine IL-1β. Inflammasome priming and assembly was time- and dose-dependent in inflammasome-reporter THP-1-ASC-GFP cells, and consistent across PM2.5 samples of variable chemical composition. While inflammasome activation was promoted by different PM2.5 surrogates, significant IL-1β release could only be observed after stimulation with transition-metal rich Residual Oil Fly Ash (ROFA) particles. This effect was confirmed in primary human monocyte-derived macrophages and murine bone marrow-derived macrophages (BMDMs), and by confocal imaging of inflammasome-reporter ASC-Citrine BMDMs. IL-1β release by ROFA was dependent on the NLRP3 inflammasome, as indicated by lack of IL-1β production in ROFA-exposed NLRP3-deficient (Nlrp3−/−) BMDMs, and by specific NLRP3 inhibition with the pharmacological compound MCC950. In addition, while ROFA promoted the upregulation of pro-inflammatory gene expression and cytokines release, MCC950 reduced TNF-α, IL-6, and CCL2 production. Furthermore, inhibition of TNF-α with a neutralizing antibody decreased IL-1β release in ROFA-exposed BMDMs. Using electron tomography, ROFA particles were observed inside intracellular vesicles and mitochondria, which showed signs of ultrastructural damage. Mechanistically, we identified lysosomal rupture, K+ efflux, and impaired mitochondrial function as important prerequisites for ROFA-mediated IL-1β release. Interestingly, specific inhibition of superoxide anion production (O2•-) from mitochondrial respiratory Complex I, but not III, blunted IL-1β release in ROFA-exposed BMDMs. Our findings unravel the mechanism by which PM2.5 promotes IL-1β release in macrophages and provide a novel link between innate immune response and exposure to air pollution PM2.5.
Fil: Caceres, Lourdes Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Abogunloko, Tijani. Albert Ludwigs University of Freiburg; Alemania
Fil: Malchow, Sara. Albert Ludwigs University of Freiburg; Alemania
Fil: Ehret, Fabienne. Albert Ludwigs University of Freiburg; Alemania
Fil: Merz, Julian. Albert Ludwigs University of Freiburg; Alemania
Fil: Li, Xiaowei. Albert Ludwigs University of Freiburg; Alemania
Fil: Sol Mitre, Lucia. Albert Ludwigs University of Freiburg; Alemania
Fil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Fil: Tasat, Deborah Ruth. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Tecnologias Emergentes y Ciencias Aplicadas. - Universidad Nacional de San Martin. Instituto de Tecnologias Emergentes y Ciencias Aplicadas.; Argentina
Fil: Mwinyella, Timothy. Albert Ludwigs University of Freiburg; Alemania
Fil: Spiga, Lisa. Albert Ludwigs University of Freiburg; Alemania
Fil: Suchanek, Dymphie. Albert Ludwigs University of Freiburg; Alemania
Fil: Fischer, Larissa. Albert Ludwigs University of Freiburg; Alemania
Fil: Gorka, Oliver. Albert Ludwigs University of Freiburg; Alemania
Fil: Colin Gissler, Mark. Albert Ludwigs University of Freiburg; Alemania
Fil: Hilgendorf, Ingo. Albert Ludwigs University of Freiburg; Alemania
Fil: Stachon, Peter. Albert Ludwigs University of Freiburg; Alemania
Fil: Rog Zielinska, Eva. Albert Ludwigs University of Freiburg; Alemania
Fil: Groß, Olaf. Albert Ludwigs University of Freiburg; Alemania
Fil: Westermann, Dirk. Albert Ludwigs University of Freiburg; Alemania
Fil: Evelson, Pablo Andrés. Albert Ludwigs University of Freiburg; Alemania
Fil: Wolf, Dennis. Albert Ludwigs University of Freiburg; Alemania
Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
description Exposure to air pollution fine particulate matter (PM2.5) aggravates respiratory and cardiovascular diseases. It has been proposed that PM2.5 uptake by alveolar macrophages promotes local inflammation that ignites a systemic response, but precise underlying mechanisms remain unclear. Here, we demonstrate that PM2.5 phagocytosis leads to NLRP3 inflammasome activation and subsequent release of the pro-inflammatory master cytokine IL-1β. Inflammasome priming and assembly was time- and dose-dependent in inflammasome-reporter THP-1-ASC-GFP cells, and consistent across PM2.5 samples of variable chemical composition. While inflammasome activation was promoted by different PM2.5 surrogates, significant IL-1β release could only be observed after stimulation with transition-metal rich Residual Oil Fly Ash (ROFA) particles. This effect was confirmed in primary human monocyte-derived macrophages and murine bone marrow-derived macrophages (BMDMs), and by confocal imaging of inflammasome-reporter ASC-Citrine BMDMs. IL-1β release by ROFA was dependent on the NLRP3 inflammasome, as indicated by lack of IL-1β production in ROFA-exposed NLRP3-deficient (Nlrp3−/−) BMDMs, and by specific NLRP3 inhibition with the pharmacological compound MCC950. In addition, while ROFA promoted the upregulation of pro-inflammatory gene expression and cytokines release, MCC950 reduced TNF-α, IL-6, and CCL2 production. Furthermore, inhibition of TNF-α with a neutralizing antibody decreased IL-1β release in ROFA-exposed BMDMs. Using electron tomography, ROFA particles were observed inside intracellular vesicles and mitochondria, which showed signs of ultrastructural damage. Mechanistically, we identified lysosomal rupture, K+ efflux, and impaired mitochondrial function as important prerequisites for ROFA-mediated IL-1β release. Interestingly, specific inhibition of superoxide anion production (O2•-) from mitochondrial respiratory Complex I, but not III, blunted IL-1β release in ROFA-exposed BMDMs. Our findings unravel the mechanism by which PM2.5 promotes IL-1β release in macrophages and provide a novel link between innate immune response and exposure to air pollution PM2.5.
publishDate 2023
dc.date.none.fl_str_mv 2023-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/227977
Caceres, Lourdes Catalina; Abogunloko, Tijani; Malchow, Sara; Ehret, Fabienne; Merz, Julian; et al.; Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages; Elsevier; Environmental Pollution; 341; 11-2023; 122997-123009
0269-7491
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227977
identifier_str_mv Caceres, Lourdes Catalina; Abogunloko, Tijani; Malchow, Sara; Ehret, Fabienne; Merz, Julian; et al.; Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PM2.5)-primed macrophages; Elsevier; Environmental Pollution; 341; 11-2023; 122997-123009
0269-7491
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0269749123019991
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.envpol.2023.122997
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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