Inflammatory role of extracellular sphingolipids in Cystic Fibrosis
Aida Zulueta1, Valeria Peli1, Michele Dei Cas1
1Biochemistry and Molecular Biology Lab., Health Sciences Department, University of Milan, Via A. di Rudinì, 8, Milan, Italy.
Abstract:
Ceramide is emerging as one of the players of inflammation in lung diseases. However, data on its inflammatory role in Cystic Fibrosis (CF) as part of the extracellular machinery driven by lung mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are missing. We obtained an in vitro model of CF-MSC by treating control human lung MSCs with a specific CFTR inhibitor. We characterized EVs populations derived from MSCs (ctr EVs) and CF-MSCs (CF-EVs) and analyzed their sphingolipid profile by LC-MS/MS. To evaluate their immunomodulatory function, we treated an in vitro human model of CF, with both EVs populations. Our data show that the two EVs populations differ for the average size, amount, and rate of uptake. CF-EVs display higher ceramide and dihydroceramide accumulation as compared to control EVs, suggesting the involvement of the de novo biosynthesis pathway in the parental CF-MSCs. Higher sphingomyelinase activity in CF-MSCs, driven by inflammation-induced ceramide accumulation, sustains the exocytosis of vesicles that export new formed pro-inflammatory ceramide. Our results suggest that CFTR dysfunction associates with an enhanced sphingolipid metabolism leading to the release of EVs that export the excess of pro-inflammatory Cer to the recipient cells, thus contributing to maintain the unresolved inflammatory status of CF.
More Related Videos
08:00Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
18:25Live Imaging Assay for Assessing the Roles of Ca2+ and Sphingomyelinase in the Repair of Pore-forming Toxin Wounds
Published on: August 25, 2013
Related Concept Videos
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
Cystic Fibrosis: Management
Sinus disease and chronic...
Regulation of Hematopoietic Stem Cells
Asymmetric Lipid Bilayer
Membrane Lipids
Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin are the most common phospholipids present in mammalian membranes. At physiological pH, phosphatidylserine is negatively charged, while the other three...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
