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Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis

Fibrotic Interstitial lung diseases (ILDs) are complex disorders of variable clinical behaviour. The majority of them cause significant morbidity, whilst Idiopathic Pulmonary Fibrosis (IPF) is recognised as the most relentless. NLRP3, AIM2, and NLRC4 inflammasomes are multiprotein complexes driving...

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Autores principales: Trachalaki, Athina, Tsitoura, Eliza, Mastrodimou, Semeli, Invernizzi, Rachele, Vasarmidi, Eirini, Bibaki, Eleni, Tzanakis, Nikolaos, Molyneaux, Philip L., Maher, Toby M., Antoniou, Katerina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248801/
https://www.ncbi.nlm.nih.gov/pubmed/34220810
http://dx.doi.org/10.3389/fimmu.2021.661811
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author Trachalaki, Athina
Tsitoura, Eliza
Mastrodimou, Semeli
Invernizzi, Rachele
Vasarmidi, Eirini
Bibaki, Eleni
Tzanakis, Nikolaos
Molyneaux, Philip L.
Maher, Toby M.
Antoniou, Katerina
author_facet Trachalaki, Athina
Tsitoura, Eliza
Mastrodimou, Semeli
Invernizzi, Rachele
Vasarmidi, Eirini
Bibaki, Eleni
Tzanakis, Nikolaos
Molyneaux, Philip L.
Maher, Toby M.
Antoniou, Katerina
author_sort Trachalaki, Athina
collection PubMed
description Fibrotic Interstitial lung diseases (ILDs) are complex disorders of variable clinical behaviour. The majority of them cause significant morbidity, whilst Idiopathic Pulmonary Fibrosis (IPF) is recognised as the most relentless. NLRP3, AIM2, and NLRC4 inflammasomes are multiprotein complexes driving IL-1β release; a proinflammatory and profibrotic cytokine. Several pathogenetic factors associated with IPF are identified as inflammasome activators, including increases in mtROS and bacterial burden. Mitochondrial oxidation and alterations in bacterial burden in IPF and other ILDs may lead to augmented inflammasome activity in airway macrophages (AMs). IPF (n=14), non-IPF-ILDs (n=12) patients and healthy subjects (n=12) were prospectively recruited and AMs were isolated from bronchoalveolar lavage. IL-1β release resulting from NLRP3, AIM2 and NLRC4 inflammasomes stimulation in AMs were determined and baseline levels of mitochondrial ROS and microbial burden were also measured. Our results showed that NLRP3 was more inducible in IPF and other ILDs compared to controls. Additionally, following AIM2 activation IL-1β release was significantly higher in IPF compared to controls, whereas similar trends were observed in Non-IPF-ILDs. NLRC4 activation was similar across groups. mtROS was significantly associated with heightened NLRP3 and AIM2 activation, and mitochondrial antioxidant treatment limited inflammasome activation. Importantly, microbial burden was linked to baseline IL-1β release and AIM2 and IL-18 relative expression independently of mtROS. In conclusion, the above findings suggested a link between the overactivation of NLRP3 and AIM2 inflammasomes, driven by mitochondrial oxidation, in the pathogenesis of lung fibrosis while changes in the microbiota may prime the inflammasome in the lungs.
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spelling pubmed-82488012021-07-02 Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis Trachalaki, Athina Tsitoura, Eliza Mastrodimou, Semeli Invernizzi, Rachele Vasarmidi, Eirini Bibaki, Eleni Tzanakis, Nikolaos Molyneaux, Philip L. Maher, Toby M. Antoniou, Katerina Front Immunol Immunology Fibrotic Interstitial lung diseases (ILDs) are complex disorders of variable clinical behaviour. The majority of them cause significant morbidity, whilst Idiopathic Pulmonary Fibrosis (IPF) is recognised as the most relentless. NLRP3, AIM2, and NLRC4 inflammasomes are multiprotein complexes driving IL-1β release; a proinflammatory and profibrotic cytokine. Several pathogenetic factors associated with IPF are identified as inflammasome activators, including increases in mtROS and bacterial burden. Mitochondrial oxidation and alterations in bacterial burden in IPF and other ILDs may lead to augmented inflammasome activity in airway macrophages (AMs). IPF (n=14), non-IPF-ILDs (n=12) patients and healthy subjects (n=12) were prospectively recruited and AMs were isolated from bronchoalveolar lavage. IL-1β release resulting from NLRP3, AIM2 and NLRC4 inflammasomes stimulation in AMs were determined and baseline levels of mitochondrial ROS and microbial burden were also measured. Our results showed that NLRP3 was more inducible in IPF and other ILDs compared to controls. Additionally, following AIM2 activation IL-1β release was significantly higher in IPF compared to controls, whereas similar trends were observed in Non-IPF-ILDs. NLRC4 activation was similar across groups. mtROS was significantly associated with heightened NLRP3 and AIM2 activation, and mitochondrial antioxidant treatment limited inflammasome activation. Importantly, microbial burden was linked to baseline IL-1β release and AIM2 and IL-18 relative expression independently of mtROS. In conclusion, the above findings suggested a link between the overactivation of NLRP3 and AIM2 inflammasomes, driven by mitochondrial oxidation, in the pathogenesis of lung fibrosis while changes in the microbiota may prime the inflammasome in the lungs. Frontiers Media S.A. 2021-06-15 /pmc/articles/PMC8248801/ /pubmed/34220810 http://dx.doi.org/10.3389/fimmu.2021.661811 Text en Copyright © 2021 Trachalaki, Tsitoura, Mastrodimou, Invernizzi, Vasarmidi, Bibaki, Tzanakis, Molyneaux, Maher and Antoniou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Trachalaki, Athina
Tsitoura, Eliza
Mastrodimou, Semeli
Invernizzi, Rachele
Vasarmidi, Eirini
Bibaki, Eleni
Tzanakis, Nikolaos
Molyneaux, Philip L.
Maher, Toby M.
Antoniou, Katerina
Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title_full Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title_fullStr Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title_full_unstemmed Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title_short Enhanced IL-1β Release Following NLRP3 and AIM2 Inflammasome Stimulation Is Linked to mtROS in Airway Macrophages in Pulmonary Fibrosis
title_sort enhanced il-1β release following nlrp3 and aim2 inflammasome stimulation is linked to mtros in airway macrophages in pulmonary fibrosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248801/
https://www.ncbi.nlm.nih.gov/pubmed/34220810
http://dx.doi.org/10.3389/fimmu.2021.661811
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