Myelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation

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

Research output: Contribution to journalArticle

32 Scopus citations

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 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.

Original languageEnglish (US)
Article numbere44998
JournalPLoS ONE
Volume7
Issue number9
DOIs
StatePublished - Sep 12 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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