NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 infla...

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Main Authors: Noy Nachmias, Sheila Langier, Rafael Y Brzezinski, Matan Siterman, Moshe Stark, Sara Etkin, Avital Avriel, Yehuda Schwarz, Shani Shenhar-Tsarfaty, Amir Bar-Shai
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0214622
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author Noy Nachmias
Sheila Langier
Rafael Y Brzezinski
Matan Siterman
Moshe Stark
Sara Etkin
Avital Avriel
Yehuda Schwarz
Shani Shenhar-Tsarfaty
Amir Bar-Shai
author_facet Noy Nachmias
Sheila Langier
Rafael Y Brzezinski
Matan Siterman
Moshe Stark
Sara Etkin
Avital Avriel
Yehuda Schwarz
Shani Shenhar-Tsarfaty
Amir Bar-Shai
author_sort Noy Nachmias
collection DOAJ
description BACKGROUND:Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD. The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model. METHODS:A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours. Cell viability was assessed by using XTT test. Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry. RESULTS:Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner. Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone. NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone. CONCLUSIONS:NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation. Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research.
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spelling doaj.art-19ef2a96272941539167823e914cbf882022-12-21T18:25:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01145e021462210.1371/journal.pone.0214622NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.Noy NachmiasSheila LangierRafael Y BrzezinskiMatan SitermanMoshe StarkSara EtkinAvital AvrielYehuda SchwarzShani Shenhar-TsarfatyAmir Bar-ShaiBACKGROUND:Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD. The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model. METHODS:A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours. Cell viability was assessed by using XTT test. Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry. RESULTS:Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner. Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone. NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone. CONCLUSIONS:NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation. Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research.https://doi.org/10.1371/journal.pone.0214622
spellingShingle Noy Nachmias
Sheila Langier
Rafael Y Brzezinski
Matan Siterman
Moshe Stark
Sara Etkin
Avital Avriel
Yehuda Schwarz
Shani Shenhar-Tsarfaty
Amir Bar-Shai
NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
PLoS ONE
title NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
title_full NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
title_fullStr NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
title_full_unstemmed NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
title_short NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.
title_sort nlrp3 inflammasome activity is upregulated in an in vitro model of copd exacerbation
url https://doi.org/10.1371/journal.pone.0214622
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