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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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.
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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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