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http://hdl.handle.net/1942/15466
Title: | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination. | Authors: | MAHESHWARI, Anurag JANSSENS, Kris BOGIE, Jeroen Van den Haute, C STRUYS, Tom LAMBRICHTS, Ivo Baekelandt, Veerle STINISSEN, Piet HENDRIKS, Jerome SLAETS, Leen HELLINGS, Niels |
Issue Date: | 2013 | Source: | MEDIATORS OF INFLAMMATION, 2013, p. 685317-685317 | Abstract: | Demyelination is one of the pathological hallmarks of multiple sclerosis (MS). To date, no therapy is available which directly potentiates endogenous remyelination. Interleukin-11 (IL-11), a member of the gp130 family of cytokines, is upregulated in MS lesions. Systemic IL-11 treatment was shown to ameliorate clinical symptoms in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. IL-11 modulates immune cells and protects oligodendrocytes in vitro. In this study, the cuprizone-induced demyelination mouse model was used to elucidate effects of IL-11 on de-and remyelination, independent of the immune response. Prophylactic-lentiviral-(LV-) mediated overexpression of IL-11 in mouse brain significantly limited acute demyelination, which was accompanied with the preservation of CC1(+) mature oligodendrocytes (OLs) and a decrease in microglial activation (Mac-2(+)). We further demonstrated that IL-11 directly reduces myelin phagocytosis in vitro. When IL-11 expressing LV was therapeutically applied in animals with extensive demyelination, a significant enhancement of remyelination was observed as demonstrated by Luxol Fast Blue staining and electron microscopy imaging. Our results indicate that IL-11 promotes maturation of NG2(+) OPCs into myelinating CC1(+) OLs and may thus explain the enhanced remyelination. Overall, we demonstrate that IL-11 is of therapeutic interest for MS and other demyelinating diseases by limiting demyelination and promoting remyelination. | Notes: | Hellings, N (reprint author), Hasselt Univ, Sch Life Sci, Biomed Res Inst, B-3590 Diepenbeek, Belgium. niels.hellings@uhasselt.be | Document URI: | http://hdl.handle.net/1942/15466 | ISSN: | 0962-9351 | e-ISSN: | 1466-1861 | DOI: | 10.1155/2013/685317 | ISI #: | 000320242300001 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2014 |
Appears in Collections: | Research publications |
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685317.pdf | 3.68 MB | Adobe PDF | View/Open |
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