Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells
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 lea...
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2017-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2017/1730245 |
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author | Domitilla Schiumarini Nicoletta Loberto Giulia Mancini Rosaria Bassi Paola Giussani Elena Chiricozzi Maura Samarani Silvia Munari Anna Tamanini Giulio Cabrini Giuseppe Lippi Maria Cristina Dechecchi Sandro Sonnino Massimo Aureli |
author_facet | Domitilla Schiumarini Nicoletta Loberto Giulia Mancini Rosaria Bassi Paola Giussani Elena Chiricozzi Maura Samarani Silvia Munari Anna Tamanini Giulio Cabrini Giuseppe Lippi Maria Cristina Dechecchi Sandro Sonnino Massimo Aureli |
author_sort | Domitilla Schiumarini |
collection | DOAJ |
description | 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. |
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id | doaj-art-af2909c0c2a44a82ba88345b7d4a22fa |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2017-01-01 |
publisher | Wiley |
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series | Mediators of Inflammation |
spelling | doaj-art-af2909c0c2a44a82ba88345b7d4a22fa2025-02-03T01:09:33ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/17302451730245Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial CellsDomitilla Schiumarini0Nicoletta Loberto1Giulia Mancini2Rosaria Bassi3Paola Giussani4Elena Chiricozzi5Maura Samarani6Silvia Munari7Anna Tamanini8Giulio Cabrini9Giuseppe Lippi10Maria Cristina Dechecchi11Sandro Sonnino12Massimo Aureli13Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyLaboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, ItalyLaboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, ItalyLaboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, ItalyLaboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, ItalyLaboratorio di Patologia Molecolare-Laboratorio di Chimica Clinica ed Ematologia, Dipartimento di Patologia e Diagnostica, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Civile Maggiore, Verona, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyDipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, ItalyCystic 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.http://dx.doi.org/10.1155/2017/1730245 |
spellingShingle | Domitilla Schiumarini Nicoletta Loberto Giulia Mancini Rosaria Bassi Paola Giussani Elena Chiricozzi Maura Samarani Silvia Munari Anna Tamanini Giulio Cabrini Giuseppe Lippi Maria Cristina Dechecchi Sandro Sonnino Massimo Aureli Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells Mediators of Inflammation |
title | Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells |
title_full | Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells |
title_fullStr | Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells |
title_full_unstemmed | Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells |
title_short | Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells |
title_sort | evidence for the involvement of lipid rafts and plasma membrane sphingolipid hydrolases in pseudomonas aeruginosa infection of cystic fibrosis bronchial epithelial cells |
url | http://dx.doi.org/10.1155/2017/1730245 |
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