Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/23716
Title: | Active liver X receptor signaling in phagocytes in multiple sclerosis lesions | Authors: | MAILLEUX, Jo VANMIERLO, Tim BOGIE, Jeroen WOUTERS, Elien Lütjohann, Dieter HENDRIKS, Jerome VAN HORSSEN, Jack |
Issue Date: | 2018 | Source: | Multiple Sclerosis Journal, 24 (3), p. 279-289 | Abstract: | Objective: We sought to determine the LXR ligands present in human macrophages after myelin phagocytosis and whether LXRs are activated in MS lesions. Methods: We used real-time quantitative PCR and immunohistochemistry to determine expression of LXRs and their response genes in human phagocytes after myelin phagocytosis and in active MS lesions. We used gas chromatographic/mass spectrometric analysis to determine LXR-activating oxysterols and cholesterol precursors present and formed in myelin and myelin-incubated cells, respectively. Results: Myelin induced LXR response genes ABCA1 and ABCG1 in human monocyte-derived macrophages. In active MS lesions, we found that both gene expression and protein levels of ABCA1 and APOE are upregulated in foamy phagocytes. Moreover, we found that the LXR ligand 27-hydroxycholesterol (27OHC) is significantly increased in human monocyte-derived macrophages after myelin uptake. Conclusions: LXR response genes are upregulated in phagocytes present in active MS lesions, indicating that LXRs are activated in actively demyelinating phagocytes. In addition, we have shown that myelin contains LXR ligands and that 27OHC is generated in human monocyte-derived macrophages after myelin processing. This suggests that LXRs in phagocytes in active MS lesions are activated at least partially by (oxy)sterols present in myelin and the generation thereof during myelin processing. | Notes: | Hendriks, JJA (reprint author), Hasselt Univ, Fac Med & Life Sci, Agoralaan Gebouw C, B-3590 Diepenbeek, Belgium, Jerome.hendriks@uhasselt.be | Keywords: | demyelinating diseases; multiple sclerosis; myelin sheath; phagocytes; liver X receptor; 27-hydroxycholesterol | Document URI: | http://hdl.handle.net/1942/23716 | ISSN: | 1352-4585 | e-ISSN: | 1477-0970 | DOI: | 10.1177/1352458517696595 | ISI #: | 000429327000009 | Rights: | © The Author(s), 2017. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
LXRs MS auteursversie.pdf | Peer-reviewed author version | 2.56 MB | Adobe PDF | View/Open |
mailleux2018.pdf Restricted Access | Published version | 640.6 kB | Adobe PDF | View/Open Request a copy |
SCOPUSTM
Citations
6
checked on Sep 5, 2020
WEB OF SCIENCETM
Citations
27
checked on Oct 12, 2024
Page view(s)
84
checked on Sep 7, 2022
Download(s)
450
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.