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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 F. J.
Wouters, Elien
Lütjohann, Dieter
Hendriks, Jerome J. A.
Van Horssen, Jack
Issue Date: 2017
Citation: Multiple Sclerosis Journal,, p. 1-11
Status: In Press
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.
URI: http://hdl.handle.net/1942/23716
DOI: 10.1177/1352458517696595
ISSN: 1352-4585
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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