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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9329 |
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| author | Elien Wouters Elien Grajchen Winde Jorissen Tess Dierckx Suzan Wetzels Melanie Loix Marie Paule Tulleners Bart Staels Piet Stinissen Mansour Haidar Jeroen F. J. Bogie Jerome J. A. Hendriks |
| author_facet | Elien Wouters Elien Grajchen Winde Jorissen Tess Dierckx Suzan Wetzels Melanie Loix Marie Paule Tulleners Bart Staels Piet Stinissen Mansour Haidar Jeroen F. J. Bogie Jerome J. A. Hendriks |
| author_sort | Elien Wouters |
| collection | DOAJ |
| 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 <i>PPARγ</i>, as well as the closely related nuclear receptors <i>PPARα</i> and <i>β</i> and <i>LXRα</i> and <i>β</i>, 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 <i>PPARγ</i> expression, while the expression of <i>PPARα</i> and <i>LXRα/β</i> is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in <i>PPARγ</i> expression. While a reduced <i>PPARγ</i> 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 <i>PPARγ</i> expression promotes myelin-induced foam cell formation in macrophages in MS. |
| first_indexed | 2024-03-10T14:15:23Z |
| format | Article |
| id | doaj.art-3e9a7c70616e4ba2857ddf1a15e2d9ff |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:15:23Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3e9a7c70616e4ba2857ddf1a15e2d9ff2023-11-20T23:49:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123932910.3390/ijms21239329Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple SclerosisElien Wouters0Elien Grajchen1Winde Jorissen2Tess Dierckx3Suzan Wetzels4Melanie Loix5Marie Paule Tulleners6Bart Staels7Piet Stinissen8Mansour Haidar9Jeroen F. J. Bogie10Jerome J. A. Hendriks11Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Pathology, CARIM, Maastricht University Medical Center, 6229 HX Maastricht, The NetherlandsDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumInserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, University of Lille, F-59000 Lille, FranceDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumDepartment of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, BelgiumMacrophages 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 <i>PPARγ</i>, as well as the closely related nuclear receptors <i>PPARα</i> and <i>β</i> and <i>LXRα</i> and <i>β</i>, 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 <i>PPARγ</i> expression, while the expression of <i>PPARα</i> and <i>LXRα/β</i> is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in <i>PPARγ</i> expression. While a reduced <i>PPARγ</i> 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 <i>PPARγ</i> expression promotes myelin-induced foam cell formation in macrophages in MS.https://www.mdpi.com/1422-0067/21/23/9329multiple sclerosismyelin-loaded macrophagesinflammationPPARγ |
| spellingShingle | Elien Wouters Elien Grajchen Winde Jorissen Tess Dierckx Suzan Wetzels Melanie Loix Marie Paule Tulleners Bart Staels Piet Stinissen Mansour Haidar Jeroen F. J. Bogie Jerome J. A. Hendriks Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis International Journal of Molecular Sciences multiple sclerosis myelin-loaded macrophages inflammation PPARγ |
| 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 | multiple sclerosis myelin-loaded macrophages inflammation PPARγ |
| url | https://www.mdpi.com/1422-0067/21/23/9329 |
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