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Mediators of Inflammation
Volume 2017, Article ID 1730245, 16 pages
https://doi.org/10.1155/2017/1730245
Research Article

Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells

1Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, Italy
2Laboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, Italy
3Sezione di Biochimica Clinica, Università degli Studi di Verona, Verona, Italy

Correspondence should be addressed to Nicoletta Loberto; ti.iminu@otrebol.attelocin, Maria Cristina Dechecchi; ti.otenev.rvoa@ihccehced.anitsirc, and Massimo Aureli; ti.iminu@ilerua.omissam

Received 26 April 2017; Revised 2 August 2017; Accepted 30 August 2017; Published 3 December 2017

Academic Editor: Sabine Groesh

Copyright © 2017 Domitilla Schiumarini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cystic fibrosis (CF) is the most common autosomal genetic recessive disease caused by mutations of gene encoding for the cystic fibrosis transmembrane conductance regulator. Patients with CF display a wide spectrum of symptoms, the most severe being chronic lung infection and inflammation, which lead to onset of cystic fibrosis lung disease. Several studies indicate that sphingolipids play a regulatory role in airway inflammation. The inhibition and downregulation of GBA2, the enzyme catabolizing glucosylceramide to ceramide, are associated with a significant reduction of IL-8 production in CF bronchial epithelial cells. Herein, we demonstrate that GBA2 plays a role in the proinflammatory state characterizing CF cells. We also report for the first time that Pseudomonas aeruginosa infection causes a recruitment of plasma membrane-associated glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells. This reorganization of cell membrane may be responsible for activation of a signaling cascade, culminating in aberrant inflammatory response in CF bronchial epithelial cells upon bacterial infection. Taken together, the presented data further support the role of sphingolipids and their metabolic enzymes in controlling the inflammatory response in CF.