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http://hdl.handle.net/1942/25967
Title: | Low-density lipoprotein receptor deficiency attenuates neuroinflammation through the induction of apolipoprotein | Authors: | MAILLEUX, Jo TIMMERMANS, Silke NELISSEN, Katherine VANMOL, Jasmine VANMIERLO, Tim VAN HORSSEN, Jack BOGIE, Jeroen HENDRIKS, Jerome |
Issue Date: | 2017 | Source: | Frontiers in Immunology, 8, p. 1-12 (Art N° 1701) | Abstract: | Objective: We aimed to determine the role of the low-density lipoprotein receptor (LDLr) in neuroinflammation by inducing experimental autoimmune encephalomyelitis (EAE) in ldlr knock out mice. Methods: MOG35–55 induced EAE in male and female ldlr−/− mice was assessed clinically and histopathologically. Expression of inflammatory mediators and apolipoprotein E (apoE) was investigated by qPCR. Changes in protein levels of apoE and tumor necrosis factor alpha (TNFα) were validated by western blot and ELISA, respectively. results: Ldlr−/−-attenuated EAE disease severity in female, but not in male, EAE mice marked by a reduced proinflammatory cytokine production in the central nervous system of female ldlr−/− mice. Macrophages from female ldlr−/− mice showed a similar decrease in proinflammatory mediators, an impaired capacity to phagocytose myelin and enhanced secretion of the anti-inflammatory apoE. Interestingly, apoE/ldlr double knock out abrogated the beneficial effect of ldlr depletion in EAE. conclusion: Collectively, we show that ldlr−/− reduces EAE disease severity in female but not in male EAE mice, and that this can be explained by increased levels of apoE in female ldlr−/− mice. Although the reason for the observed sexual dimorphism remains unclear, our findings show that LDLr and associated apoE levels are involved in neuroinflammatory processes. | Keywords: | neuroinflammation; multiple sclerosis; experimental autoimmune encephalomyelitis; low-density lipoprotein receptor; apolipoprotein E | Document URI: | http://hdl.handle.net/1942/25967 | ISSN: | 1664-3224 | e-ISSN: | 1664-3224 | DOI: | 10.3389/fimmu.2017.01701 | ISI #: | 000416523900001 | Rights: | Copyright © 2017 Mailleux, Timmermans, Nelissen, Vanmol, Vanmierlo, van Horssen, Bogie and Hendriks. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2018 |
Appears in Collections: | Research publications |
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Frontiers in imm 2017 .pdf | Published version | 2.38 MB | Adobe PDF | View/Open |
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