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Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584994/ https://www.ncbi.nlm.nih.gov/pubmed/31221118 http://dx.doi.org/10.1186/s12890-019-0876-9 |
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author | Shikano, Sotaro Gon, Yasuhiro Maruoka, Shuichiro Shimizu, Tetsuo Kozu, Yutaka Iida, Yuko Hikichi, Mari Takahashi, Mai Okamoto, Shinichi Tsuya, Kota Fukuda, Asami Mizumura, Kenji Hashimoto, Shu |
author_facet | Shikano, Sotaro Gon, Yasuhiro Maruoka, Shuichiro Shimizu, Tetsuo Kozu, Yutaka Iida, Yuko Hikichi, Mari Takahashi, Mai Okamoto, Shinichi Tsuya, Kota Fukuda, Asami Mizumura, Kenji Hashimoto, Shu |
author_sort | Shikano, Sotaro |
collection | PubMed |
description | BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. METHODS: Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. RESULTS: Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1β) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1β expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. CONCLUSIONS: These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS. |
format | Online Article Text |
id | pubmed-6584994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65849942019-06-27 Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS Shikano, Sotaro Gon, Yasuhiro Maruoka, Shuichiro Shimizu, Tetsuo Kozu, Yutaka Iida, Yuko Hikichi, Mari Takahashi, Mai Okamoto, Shinichi Tsuya, Kota Fukuda, Asami Mizumura, Kenji Hashimoto, Shu BMC Pulm Med Research Article BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. METHODS: Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. RESULTS: Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1β) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1β expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. CONCLUSIONS: These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS. BioMed Central 2019-06-20 /pmc/articles/PMC6584994/ /pubmed/31221118 http://dx.doi.org/10.1186/s12890-019-0876-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Shikano, Sotaro Gon, Yasuhiro Maruoka, Shuichiro Shimizu, Tetsuo Kozu, Yutaka Iida, Yuko Hikichi, Mari Takahashi, Mai Okamoto, Shinichi Tsuya, Kota Fukuda, Asami Mizumura, Kenji Hashimoto, Shu Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title | Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title_full | Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title_fullStr | Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title_full_unstemmed | Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title_short | Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS |
title_sort | increased extracellular vesicle mirna-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ards |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584994/ https://www.ncbi.nlm.nih.gov/pubmed/31221118 http://dx.doi.org/10.1186/s12890-019-0876-9 |
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