Extracellular Vesicles Induce Nuclear Factor-κB Activation and Interleukin-8 Synthesis through miRNA-191-5p Contributing to Inflammatory Processes: Potential Implications in the Pathogenesis of Chronic Obstructive Pulmonary Disease
Sara Carpi,
Beatrice Polini,
Dario Nieri,
Stefano Doccini,
Maria Conti,
Erika Bazzan,
Marta Pagnini,
Filippo Maria Santorelli,
Marco Cecchini,
Paola Nieri,
Alessandro Celi,
Tommaso Neri
Affiliations
Sara Carpi
Department of Health Sciences, University ‘Magna Græcia’ of Catanzaro, 88100 Catanzaro, Italy
Beatrice Polini
Department of Pathology, University of Pisa, 56100 Pisa, Italy
Dario Nieri
Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy
Stefano Doccini
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
Maria Conti
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy
Erika Bazzan
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy
Marta Pagnini
Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy
Filippo Maria Santorelli
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
Marco Cecchini
NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy
Paola Nieri
Department of Pharmacy, University of Pisa, 56100 Pisa, Italy
Alessandro Celi
Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy
Tommaso Neri
Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy
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-κB 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-κB 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.
