Myelin-derived lipids modulate macrophage activity by liver X receptor activation.
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 de...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3440367?pdf=render |
| _version_ | 1831683673330548736 |
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| author | Jeroen F J Bogie Silke Timmermans Vân Anh Huynh-Thu Alexandre Irrthum Hubert J M Smeets Jan-Åke Gustafsson Knut R Steffensen Monique Mulder Piet Stinissen Niels Hellings Jerome J A Hendriks |
| author_facet | Jeroen F J Bogie Silke Timmermans Vân Anh Huynh-Thu Alexandre Irrthum Hubert J M Smeets Jan-Åke Gustafsson Knut R Steffensen Monique Mulder Piet Stinissen Niels Hellings Jerome J A Hendriks |
| author_sort | Jeroen F J Bogie |
| collection | DOAJ |
| description | 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 signaling 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. |
| first_indexed | 2024-12-20T06:41:32Z |
| format | Article |
| id | doaj.art-5aafb65e5a5b4dbea6049ae2cc79c7b5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T06:41:32Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5aafb65e5a5b4dbea6049ae2cc79c7b52022-12-21T19:49:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4499810.1371/journal.pone.0044998Myelin-derived lipids modulate macrophage activity by liver X receptor activation.Jeroen F J BogieSilke TimmermansVân Anh Huynh-ThuAlexandre IrrthumHubert J M SmeetsJan-Åke GustafssonKnut R SteffensenMonique MulderPiet StinissenNiels HellingsJerome J A HendriksMultiple 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 signaling 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.http://europepmc.org/articles/PMC3440367?pdf=render |
| spellingShingle | Jeroen F J Bogie Silke Timmermans Vân Anh Huynh-Thu Alexandre Irrthum Hubert J M Smeets Jan-Åke Gustafsson Knut R Steffensen Monique Mulder Piet Stinissen Niels Hellings Jerome J A Hendriks Myelin-derived lipids modulate macrophage activity by liver X receptor activation. PLoS ONE |
| title | Myelin-derived lipids modulate macrophage activity by liver X receptor activation. |
| title_full | Myelin-derived lipids modulate macrophage activity by liver X receptor activation. |
| title_fullStr | Myelin-derived lipids modulate macrophage activity by liver X receptor activation. |
| title_full_unstemmed | Myelin-derived lipids modulate macrophage activity by liver X receptor activation. |
| title_short | Myelin-derived lipids modulate macrophage activity by liver X receptor activation. |
| title_sort | myelin derived lipids modulate macrophage activity by liver x receptor activation |
| url | http://europepmc.org/articles/PMC3440367?pdf=render |
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