PMID- 31221118 OWN - NLM STAT- MEDLINE DCOM- 20191218 LR - 20201209 IS - 1471-2466 (Electronic) IS - 1471-2466 (Linking) VI - 19 IP - 1 DP - 2019 Jun 20 TI - Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS. PG - 110 LID - 10.1186/s12890-019-0876-9 [doi] LID - 110 AB - 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-1beta) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1beta 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. FAU - Shikano, Sotaro AU - Shikano S AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Gon, Yasuhiro AU - Gon Y AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Maruoka, Shuichiro AU - Maruoka S AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Shimizu, Tetsuo AU - Shimizu T AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Kozu, Yutaka AU - Kozu Y AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Iida, Yuko AU - Iida Y AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Hikichi, Mari AU - Hikichi M AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Takahashi, Mai AU - Takahashi M AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Okamoto, Shinichi AU - Okamoto S AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Tsuya, Kota AU - Tsuya K AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Fukuda, Asami AU - Fukuda A AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. FAU - Mizumura, Kenji AU - Mizumura K AUID- ORCID: 0000-0001-8532-9670 AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. mizumura.kenji@nihon-u.ac.jp. FAU - Hashimoto, Shu AU - Hashimoto S AD - Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. LA - eng GR - 15K09196/Japan Society for the Promotion of Science/ GR - S1511014/Strategic Research Foundation for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology of Japan/ PT - Journal Article DEP - 20190620 PL - England TA - BMC Pulm Med JT - BMC pulmonary medicine JID - 100968563 RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (MicroRNAs) RN - 0 (Mirn466 microRNA, mouse) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) SB - IM MH - Animals MH - Bronchoalveolar Lavage Fluid/chemistry MH - Disease Models, Animal MH - Extracellular Vesicles/*metabolism MH - Inflammasomes/*metabolism MH - Inflammation/metabolism MH - Interleukin-1beta/metabolism MH - Lipopolysaccharides MH - Macrophages/drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Precipitating Factors MH - Respiratory Distress Syndrome/chemically induced/*metabolism PMC - PMC6584994 OTO - NOTNLM OT - ARDS OT - Extracellular vesicles OT - NLRP3 inflammasome OT - miRNA COIS- The authors declare that they have no competing interests. EDAT- 2019/06/22 06:00 MHDA- 2019/12/19 06:00 PMCR- 2019/06/20 CRDT- 2019/06/22 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2019/06/11 00:00 [accepted] PHST- 2019/06/22 06:00 [entrez] PHST- 2019/06/22 06:00 [pubmed] PHST- 2019/12/19 06:00 [medline] PHST- 2019/06/20 00:00 [pmc-release] AID - 10.1186/s12890-019-0876-9 [pii] AID - 876 [pii] AID - 10.1186/s12890-019-0876-9 [doi] PST - epublish SO - BMC Pulm Med. 2019 Jun 20;19(1):110. doi: 10.1186/s12890-019-0876-9.