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Article

Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis

1
Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium
2
Department of Pathology, CARIM, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands
3
Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, University of Lille, F-59000 Lille, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9329; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239329
Received: 26 November 2020 / Accepted: 3 December 2020 / Published: 7 December 2020
(This article belongs to the Special Issue Molecular Mechanisms Underlying CNS Inflammation)
Macrophages play a crucial role during the pathogenesis of multiple sclerosis (MS), a neuroinflammatory autoimmune disorder of the central nervous system. Important regulators of the metabolic and inflammatory phenotype of macrophages are liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). Previously, it has been reported that PPARγ expression is decreased in peripheral blood mononuclear cells of MS patients. The goal of the present study was to determine to what extent PPARγ, as well as the closely related nuclear receptors PPARα and β and LXRα and β, are differentially expressed in monocytes from MS patients and how this change in expression affects the function of monocyte-derived macrophages. We demonstrate that monocytes of relapsing-remitting MS patients display a marked decrease in PPARγ expression, while the expression of PPARα and LXRα/β is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in PPARγ expression. While a reduced PPARγ expression did not affect the inflammatory and phagocytic properties of myelin-loaded macrophages, it did impact myelin processing by increasing the intracellular cholesterol load of myelin-phagocytosing macrophages. Collectively, our findings indicate that an inflammation-induced reduction in PPARγ expression promotes myelin-induced foam cell formation in macrophages in MS. View Full-Text
Keywords: multiple sclerosis; myelin-loaded macrophages; inflammation; PPARγ multiple sclerosis; myelin-loaded macrophages; inflammation; PPARγ
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MDPI and ACS Style

Wouters, E.; Grajchen, E.; Jorissen, W.; Dierckx, T.; Wetzels, S.; Loix, M.; Tulleners, M.P.; Staels, B.; Stinissen, P.; Haidar, M.; Bogie, J.F.J.; Hendriks, J.J.A. Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis. Int. J. Mol. Sci. 2020, 21, 9329. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239329

AMA Style

Wouters E, Grajchen E, Jorissen W, Dierckx T, Wetzels S, Loix M, Tulleners MP, Staels B, Stinissen P, Haidar M, Bogie JFJ, Hendriks JJA. Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis. International Journal of Molecular Sciences. 2020; 21(23):9329. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239329

Chicago/Turabian Style

Wouters, Elien, Elien Grajchen, Winde Jorissen, Tess Dierckx, Suzan Wetzels, Melanie Loix, Marie P. Tulleners, Bart Staels, Piet Stinissen, Mansour Haidar, Jeroen F.J. Bogie, and Jerome J.A. Hendriks 2020. "Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis" International Journal of Molecular Sciences 21, no. 23: 9329. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239329

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