Autor: |
Carpi S; Department of Health Sciences, University 'Magna Græcia' of Catanzaro, 88100 Catanzaro, Italy.; NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy., Polini B; Department of Pathology, University of Pisa, 56100 Pisa, Italy., Nieri D; Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy., Doccini S; Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy., Conti M; Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy., Bazzan E; Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padua, Italy., Pagnini M; Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy., Santorelli FM; Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy., Cecchini M; NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy., Nieri P; Department of Pharmacy, University of Pisa, 56100 Pisa, Italy., Celi A; Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy., Neri T; Centre for Cardio-Respiratory Cell Biology, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56100 Pisa, Italy. |
Abstrakt: |
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. |