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

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-activate...

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Autores principales: Wouters, Elien, Grajchen, Elien, Jorissen, Winde, Dierckx, Tess, Wetzels, Suzan, Loix, Melanie, Tulleners, Marie Paule, Staels, Bart, Stinissen, Piet, Haidar, Mansour, Bogie, Jeroen F.J., Hendriks, Jerome J.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731422/
https://www.ncbi.nlm.nih.gov/pubmed/33297574
http://dx.doi.org/10.3390/ijms21239329
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author Wouters, Elien
Grajchen, Elien
Jorissen, Winde
Dierckx, Tess
Wetzels, Suzan
Loix, Melanie
Tulleners, Marie Paule
Staels, Bart
Stinissen, Piet
Haidar, Mansour
Bogie, Jeroen F.J.
Hendriks, Jerome J.A.
author_facet Wouters, Elien
Grajchen, Elien
Jorissen, Winde
Dierckx, Tess
Wetzels, Suzan
Loix, Melanie
Tulleners, Marie Paule
Staels, Bart
Stinissen, Piet
Haidar, Mansour
Bogie, Jeroen F.J.
Hendriks, Jerome J.A.
author_sort Wouters, Elien
collection PubMed
description 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.
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spelling pubmed-77314222020-12-12 Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis Wouters, Elien Grajchen, Elien Jorissen, Winde Dierckx, Tess Wetzels, Suzan Loix, Melanie Tulleners, Marie Paule Staels, Bart Stinissen, Piet Haidar, Mansour Bogie, Jeroen F.J. Hendriks, Jerome J.A. Int J Mol Sci Article 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. MDPI 2020-12-07 /pmc/articles/PMC7731422/ /pubmed/33297574 http://dx.doi.org/10.3390/ijms21239329 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wouters, Elien
Grajchen, Elien
Jorissen, Winde
Dierckx, Tess
Wetzels, Suzan
Loix, Melanie
Tulleners, Marie Paule
Staels, Bart
Stinissen, Piet
Haidar, Mansour
Bogie, Jeroen F.J.
Hendriks, Jerome J.A.
Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title_full Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title_fullStr Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title_full_unstemmed Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title_short Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis
title_sort altered pparγ expression promotes myelin-induced foam cell formation in macrophages in multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731422/
https://www.ncbi.nlm.nih.gov/pubmed/33297574
http://dx.doi.org/10.3390/ijms21239329
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