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Please use this identifier to cite or link to this item: 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
Citation: 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
URI: http://hdl.handle.net/1942/15466
DOI: 10.1155/2013/685317
ISI #: 000320242300001
ISSN: 0962-9351
Category: A1
Type: Journal Contribution
Validation: ecoom, 2014
Appears in Collections: Research publications

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