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

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2024-08, Vol.14 (8), p.1030
• Main Authors: Carpi, Sara, Polini, Beatrice, Nieri, Dario, Doccini, Stefano, Conti, Maria, Bazzan, Erika, Pagnini, Marta, Santorelli, Filippo Maria, Cecchini, Marco, Nieri, Paola, Celi, Alessandro, Neri, Tommaso
• Format: Article
• Language: English
• Subjects: Aged; B cells; Bronchi - metabolism; Bronchi - pathology; Cell activation; Cell culture; Cell Line; Chronic obstructive pulmonary disease; Cytokines; Epithelial cells; Epithelial Cells - metabolism; Extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Female; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Interleukin 8; Interleukin-8 - genetics; Interleukin-8 - metabolism; Interleukins; Lung diseases; Lung diseases, Obstructive; Male; MicroRNA; microRNA-191; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; NF-kappa B - metabolism; NF-κB protein; nuclear factor-κB; Pathogenesis; Peripheral blood; Plasma; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Respiratory tract diseases; Signal Transduction; Tiotropium; Transcription factors
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14081030

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.