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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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