Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/13936
Title: Myelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation
Authors: BOGIE, Jeroen 
TIMMERMANS, Silke 
Huynh-Thu, V.
Irrthum, A.
Smeets, H.J.M.
Gustafsson, J.A.
Steffensen, K.R.
Mulder, M.T.
STINISSEN, Piet 
HELLINGS, Niels 
HENDRIKS, Jerome 
Issue Date: 2012
Source: PLoS One, 7 (9): e44998
Abstract: Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing degenerated myelin, are abundantly found in active multiple sclerosis lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes involved in migration, phagocytosis and inflammation. Interestingly, myelin internalization also induced the expression of genes involved in liver-X-receptor signalling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. In addition, myelin suppresses the secretion of the pro-inflammatory mediator IL-6 by macrophages, which was mediated by activation of liver-X-receptor β. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in demyelinating diseases such as multiple sclerosis.
Document URI: http://hdl.handle.net/1942/13936
ISSN: 1932-6203
e-ISSN: 1932-6203
DOI: 10.1371/journal.pone.0044998
ISI #: 000308738500104
Rights: © 2012 Bogie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Category: A1
Type: Journal Contribution
Validations: ecoom 2013
Appears in Collections:Research publications

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