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http://hdl.handle.net/1942/16494
Title: | Myelin alters the inflammatory phenotype of macrophages by activating PPARs | Authors: | BOGIE, Jeroen JORISSEN, Winde MAILLEUX, Jo Nijland, G. Philip Zelcer, Noam VANMIERLO, Tim VAN HORSSEN, Jack STINISSEN, Piet HELLINGS, Niels HENDRIKS, Jerome |
Issue Date: | 2013 | Source: | Acta Neuropathologica Communications, 1 (43), p. 1-13 | Abstract: | Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPARβ/δ is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPARβ/δ in macrophages in the human brain. Conclusion Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPARβ/δ activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics. | Keywords: | macrophages; myelin; multiple sclerosis; phosphatidylserine; PPAR; neuroinflammation | Document URI: | http://hdl.handle.net/1942/16494 | ISSN: | 0001-6322 | e-ISSN: | 1432-0533 | DOI: | 10.1186/2051-5960-1-43 | Rights: | © 2013 Bogie et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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Bogie Jorissen 2013 myelin altersinflammatory.pdf | Published version | 3.11 MB | Adobe PDF | View/Open |
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