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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/25758

Title: Low-Density Lipoprotein Receptor Deficiency Attenuates Neuroinflammation through the Induction of Apolipoprotein E
Authors: Mailleux, Jo
Timmermans, Silke
Nelissen, Katherine
Vanmol, Jasmine
Vanmierlo, Tim
van Horssen, Jack
Bogie, Jeroen F. J.
Hendriks, Jerome J. A.
Issue Date: 2017
Publisher: FRONTIERS MEDIA SA
Citation: 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: MOG(35-55) 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 (TNF alpha) 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.
Notes: [Mailleux, Jo; Timmermans, Silke; Nelissen, Katherine; Vanmol, Jasmine; Vanmierlo, Tim; Bogie, Jeroen F. J.; Hendriks, Jerome J. A.] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. [van Horssen, Jack] Vrije Univ Amsterdam, Mol Cell Biol & Immunol, Med Ctr, Amsterdam, Netherlands.
URI: http://hdl.handle.net/1942/25758
DOI: 10.3389/fimmu.2017.01701
ISI #: 000416523900001
ISSN: 1664-3224
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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