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Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition.

Sewell, GW; Hannun, YA; Han, X; Koster, G; Bielawski, J; Goss, V; Smith, PJ; ... Segal, AW; + view all (2012) Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition. Int J Biochem Cell Biol , 44 (11) 1839 - 1846. 10.1016/j.biocel.2012.06.016. Green open access

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Abstract

Crohn's disease is a chronic inflammatory condition largely affecting the terminal ileum and large bowel. A contributing cause is the failure of an adequate acute inflammatory response as a result of impaired secretion of pro-inflammatory cytokines by macrophages. This defective secretion arises from aberrant vesicle trafficking, misdirecting the cytokines to lysosomal degradation. Aberrant intestinal permeability is also well-established in Crohn's disease. Both the disordered vesicle trafficking and increased bowel permeability could result from abnormal lipid composition. We thus measured the sphingo- and phospholipid composition of macrophages, using mass spectrometry and stable isotope labelling approaches. Stimulation of macrophages with heat-killed Escherichia coli resulted in three main changes; a significant reduction in the amount of individual ceramide species, an altered composition of phosphatidylcholine, and an increased rate of phosphatidylcholine synthesis in macrophages. These changes were observed in macrophages from both healthy control individuals and patients with Crohn's disease. The only difference detected between control and Crohn's disease macrophages was a reduced proportion of newly-synthesised phosphatidylinositol 16:0/18:1 over a defined time period. Shotgun lipidomics analysis of macroscopically non-inflamed ileal biopsies showed a significant decrease in this same lipid species with overall preservation of sphingolipid, phospholipid and cholesterol composition.

Type: Article
Title: Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition.
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biocel.2012.06.016
Publisher version: http://dx.doi.org/10.1016/j.biocel.2012.06.016
Language: English
Additional information: © 2012 Published by Elsevier Ltd. All rights reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License. PMCID: PMC3778899
Keywords: Adult, Biopsy, Case-Control Studies, Ceramides, Crohn Disease, Demography, Escherichia coli, Female, Humans, Ileum, Macrophages, Male, Metabolomics, Middle Aged, Phosphatidylcholines, Phosphatidylinositols, Phosphatidylserines, Sphingolipids
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/1352049
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