TY - JOUR
T1 - NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation
AU - Nachmias, Noy
AU - Langier, Sheila
AU - Brzezinski, Rafael Y.
AU - Siterman, Matan
AU - Stark, Moshe
AU - Etkin, Sara
AU - Avriel, Avital
AU - Schwarz, Yehuda
AU - Shenhar-Tsarfaty, Shani
AU - Bar-Shai, Amir
N1 - Publisher Copyright:
© 2019 Nachmias et al. 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 credited.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85065959106
U2 - 10.1371/journal.pone.0214622
DO - 10.1371/journal.pone.0214622
M3 - Article
C2 - 31112544
AN - SCOPUS:85065959106
SN - 1932-6203
VL - 14
JO - PLOS ONE
JF - PLOS ONE
IS - 5
M1 - e0214622
ER -
