{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:01:12Z","timestamp":1790010072718,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente 2024","award":["RC 5x1000"],"award-info":[{"award-number":["RC 5x1000"]}]},{"name":"Italian Ministry of Health","award":["RC 5x1000"],"award-info":[{"award-number":["RC 5x1000"]}]},{"name":"University of Pisa \u201cFondi di Ateneo\u201d","award":["RC 5x1000"],"award-info":[{"award-number":["RC 5x1000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Extracellular vesicles (EVs) play a pivotal role in a variety of physiologically relevant processes, including lung inflammation. Recent attention has been directed toward EV-derived microRNAs (miRNAs), such as miR-191-5p, particularly in the context of inflammation. Here, we investigated the impact of miR-191-5p-enriched EVs on the activation of NF-\u03baB and the expression of molecules associated with inflammation such as interleukin-8 (IL-8). To this aim, cells of bronchial epithelial origin, 16HBE, were transfected with miR-191-5p mimic and inhibitor and subsequently subjected to stimulations to generate EVs. Then, bronchial epithelial cells were exposed to the obtained EVs to evaluate the activation of NF-\u03baB and IL-8 levels. Additionally, we conducted a preliminary investigation to analyze the expression profiles of miR-191-5p in EVs isolated from the plasma of patients diagnosed with chronic obstructive pulmonary disease (COPD). Our initial findings revealed two significant observations. First, the exposure of bronchial epithelial cells to miR-191-5p-enriched EVs activated the NF-kB signaling and increased the synthesis of IL-8. Second, we discovered the presence of miR-191-5p in peripheral blood-derived EVs from COPD patients and noted a correlation between miR-191-5p levels and inflammatory and functional parameters. Collectively, these data corroborate and further expand the proinflammatory role of EVs, with a specific emphasis on miR-191-5p as a key cargo involved in this process. Consequently, we propose a model in which miR-191-5p, carried by EVs, plays a role in airway inflammation and may contribute to the pathogenesis of COPD.<\/jats:p>","DOI":"10.3390\/biom14081030","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T05:19:36Z","timestamp":1724044776000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Vesicles Induce Nuclear Factor-\u03baB Activation and Interleukin-8 Synthesis through miRNA-191-5p Contributing to Inflammatory Processes: Potential Implications in the Pathogenesis of Chronic Obstructive Pulmonary Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-9009","authenticated-orcid":false,"given":"Sara","family":"Carpi","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University \u2018Magna Gr\u00e6cia\u2019 of Catanzaro, 88100 Catanzaro, Italy"},{"name":"NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Polini","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Nieri","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-8253","authenticated-orcid":false,"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-5190","authenticated-orcid":false,"given":"Maria","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2956-0880","authenticated-orcid":false,"given":"Erika","family":"Bazzan","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Pagnini","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9062","authenticated-orcid":false,"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9688-2356","authenticated-orcid":false,"given":"Marco","family":"Cecchini","sequence":"additional","affiliation":[{"name":"NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5809-2938","authenticated-orcid":false,"given":"Paola","family":"Nieri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1364-9568","authenticated-orcid":false,"given":"Alessandro","family":"Celi","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7289-1522","authenticated-orcid":false,"given":"Tommaso","family":"Neri","sequence":"additional","affiliation":[{"name":"Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2300239","DOI":"10.1183\/13993003.00239-2023","article-title":"Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary","volume":"61","author":"Celli","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1017\/gheg.2018.1","article-title":"The unmet global burden of COPD","volume":"3","author":"Quaderi","year":"2018","journal-title":"Glob. Health Epidemiol. Genom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15076","DOI":"10.1038\/nrdp.2015.76","article-title":"Chronic obstructive pulmonary disease","volume":"1","author":"Barnes","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s41030-023-00233-z","article-title":"The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD","volume":"9","author":"Terry","year":"2023","journal-title":"Pulm. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"00850","DOI":"10.1183\/23120541.00850-2023","article-title":"Mortality prevention as the centre of COPD management","volume":"10","author":"Papaioannou","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1164\/rccm.202303-0400SO","article-title":"An Update on Outcomes for COPD Pharmacological Trials: A COPD Investigators Report\u2014Reassessment of the 2008 American Thoracic Society\/European Respiratory Society Statement on Outcomes for COPD Pharmacological Trials","volume":"208","author":"Cazzola","year":"2023","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1007\/s00018-011-0689-3","article-title":"Membrane vesicles, current state-of-the-art: Emerging role of extracellular vesicles","volume":"68","author":"Aradi","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF03257159","article-title":"The role of interleukin-8 and its receptors in inflammatory lung disease: Implications for therapy","volume":"1","author":"Pease","year":"2002","journal-title":"Am. J. Respir. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.4049\/jimmunol.177.3.1975","article-title":"Monocyte\/macrophage-derived microparticles up-regulate inflammatory mediator synthesis by human airway epithelial cells","volume":"177","author":"Cerri","year":"2006","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1183\/09031936.00023310","article-title":"Role of NF-kappaB and PPAR-gamma in lung inflammation induced by monocyte-derived microparticles","volume":"37","author":"Neri","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.yexcr.2018.02.023","article-title":"CD18-mediated adhesion is required for the induction of a proinflammatory phenotype in lung epithelial cells by mononuclear cell-derived extracellular vesicles","volume":"365","author":"Neri","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gou, Z., Yang, H., Wang, R., Wang, S., Chen, Q., Liu, Z., and Zhang, Y. (2024). A new frontier in precision medicine: Exploring the role of extracellular vesicles in chronic obstructive pulmonary disease. Biomed. Pharmacother., 174.","DOI":"10.1016\/j.biopha.2024.116443"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107563","DOI":"10.1016\/j.rmed.2024.107563","article-title":"Enhanced prothrombotic and proinflammatory activity of circulating extracellular vesicles in acute exacerbations of chronic obstructive pulmonary disease","volume":"223","author":"Nieri","year":"2024","journal-title":"Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrm2347","article-title":"Small non-coding RNAs in animal development","volume":"9","author":"Stefani","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41580-020-0251-y","article-title":"RNA delivery by extracellular vesicles in mammalian cells and its applications","volume":"21","author":"Breyne","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1515\/hsz-2017-0249","article-title":"The role of microRNAs in chronic respiratory disease: Recent insights","volume":"399","author":"Stolzenburg","year":"2018","journal-title":"Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Carpi, S., Polini, B., Nieri, D., Dubbini, N., Celi, A., Nieri, P., and Neri, T. (2020). Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease. Diagnostics, 10.","DOI":"10.3390\/diagnostics10070502"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nagpal, N., and Kulshreshtha, R. (2014). miR-191: An emerging player in disease biology. Front. Genet., 5.","DOI":"10.3389\/fgene.2014.00099"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1096\/fj.201601263R","article-title":"miR-191 suppresses angiogenesis by activation of NF-\u03baB signaling","volume":"31","author":"Gu","year":"2017","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1161\/ATVBAHA.114.305048","article-title":"Impairment of Wound Healing in Patients With Type 2 Diabetes Mellitus Influences Circulating MicroRNA Patterns via Inflammatory Cytokines","volume":"35","author":"Dangwal","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Serban, K.A., Rezania, S., Petrusca, D.N., Poirier, C., Cao, D., Justice, M.J., Patel, M., Tsvetkova, I., Kamocki, K., and Mikosz, A. (2016). Structural and functional characterization of endothelial microparticles released by cigarette smoke. Sci. Rep., 6.","DOI":"10.1038\/srep31596"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.taap.2013.05.018","article-title":"Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects","volume":"272","author":"Takahashi","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wei, C., Henderson, H., Spradley, C., Li, L., Kim, I.K., Kumar, S., Hong, N., Arroliga, A.C., and Gupta, S. (2013). Circulating miRNAs as potential marker for pulmonary hypertension. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064396"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Neri, T., Scalise, V., Passalacqua, I., Sanguinetti, C., Lombardi, S., Pergoli, L., Bollati, V., Pedrinelli, R., Paggiaro, P., and Celi, A. (2019). Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-48129-w"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1183\/09031936.05.00035005","article-title":"Standardisation of the measurement of lung volumes","volume":"26","author":"Wanger","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1164\/rccm.201908-1590ST","article-title":"Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement","volume":"200","author":"Graham","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16E0016","DOI":"10.1183\/13993003.E0016-2016","article-title":"Executive Summary: 2017 ERS\/ATS standards for single-breath carbon monoxide uptake in the lung","volume":"49","author":"Graham","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0025-7125(05)70453-3","article-title":"Diffusing capacity in the clinical assessment of chronic airflow limitation","volume":"80","author":"Cotton","year":"1996","journal-title":"Med. Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in Ingenuity Pathway Analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory mechanisms in patients with chronic obstructive pulmonary disease","volume":"138","author":"Barnes","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1042\/CS20160487","article-title":"Cellular and molecular mechanisms of asthma and COPD","volume":"131","author":"Barnes","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1056\/NEJMoa1008378","article-title":"Tiotropium versus salmeterol for the prevention of exacerbations of COPD","volume":"364","author":"Vogelmeier","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Agust\u00ed, A., Edwards, L.D., Rennard, S.I., MacNee, W., Tal-Singer, R., Miller, B.E., Vestbo, J., Lomas, D.A., Calverley, P.M.A., and Wouters, E. (2012). Persistent systemic inflammation is associated with poor clinical outcomes in COPD: A novel phenotype. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037483"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nieri, D., Daniele, M., Lombardi, S., Bazzan, E., Santerini, S., De Cusatis, G., Vagaggini, B., Cosio, M.G., Saetta, M., and Paggiaro, P. (2021). Circulating Extracellular Vesicles Are Associated with Disease Severity and Interleukin-6 Levels in COPD: A Pilot Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10215014"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.chest.2021.04.033","article-title":"Clinical and Prognostic Impact of Low Diffusing Capacity for Carbon Monoxide Values in Patients With Global Initiative for Obstructive Lung Disease I COPD","volume":"160","author":"Cabrera","year":"2021","journal-title":"Chest"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1164\/rccm.201209-1697OC","article-title":"Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study","volume":"188","author":"Thomashow","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/s41467-019-09387-4","article-title":"Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A","volume":"10","author":"Im","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1703244","DOI":"10.1080\/20013078.2019.1703244","article-title":"Inhibiting extracellular vesicles formation and release: A review of EV inhibitors","volume":"9","author":"Catalano","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jconrel.2021.10.019","article-title":"Promotion or inhibition of extracellular vesicle release: Emerging therapeutic opportunities","volume":"340","author":"Hao","year":"2021","journal-title":"J. Control. 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