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

Biomolecules. 2024 Aug 19;14(8):1030. doi: 10.3390/biom14081030.

Abstract

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.

Keywords: DLCO; chronic obstructive pulmonary disease; extracellular vesicles; inflammation; interleukin-6; interleukin-8; microRNA-191; nuclear factor-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchi / metabolism
  • Bronchi / pathology
  • Cell Line
  • Epithelial Cells / metabolism
  • Extracellular Vesicles* / genetics
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-8* / genetics
  • Interleukin-8* / metabolism
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • NF-kappa B* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / pathology
  • Signal Transduction

Substances

  • MicroRNAs
  • Interleukin-8
  • NF-kappa B
  • MIRN191 microRNA, human
  • CXCL8 protein, human