Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination
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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/685317 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562574996013056 |
|---|---|
| author | Anurag Maheshwari Kris Janssens Jeroen Bogie Chris Van Den Haute Tom Struys Ivo Lambrichts Veerle Baekelandt Piet Stinissen Jerome J. A. Hendriks Helena Slaets Niels Hellings |
| author_facet | Anurag Maheshwari Kris Janssens Jeroen Bogie Chris Van Den Haute Tom Struys Ivo Lambrichts Veerle Baekelandt Piet Stinissen Jerome J. A. Hendriks Helena Slaets Niels Hellings |
| author_sort | Anurag Maheshwari |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f117af44bd0841b69cb08aa7f8074c5a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f117af44bd0841b69cb08aa7f8074c5a2025-02-03T01:22:22ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/685317685317Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances RemyelinationAnurag Maheshwari0Kris Janssens1Jeroen Bogie2Chris Van Den Haute3Tom Struys4Ivo Lambrichts5Veerle Baekelandt6Piet Stinissen7Jerome J. A. Hendriks8Helena Slaets9Niels Hellings10Biomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumLaboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, Katholieke University of Leuven, 3000 Leuven, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumLaboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, Katholieke University of Leuven, 3000 Leuven, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumBiomedical Research Institute, School of Life Sciences, Hasselt University and Transnational University Limburg, 3590 Diepenbeek, BelgiumDemyelination 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.http://dx.doi.org/10.1155/2013/685317 |
| spellingShingle | Anurag Maheshwari Kris Janssens Jeroen Bogie Chris Van Den Haute Tom Struys Ivo Lambrichts Veerle Baekelandt Piet Stinissen Jerome J. A. Hendriks Helena Slaets Niels Hellings Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination Mediators of Inflammation |
| title | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination |
| title_full | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination |
| title_fullStr | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination |
| title_full_unstemmed | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination |
| title_short | Local Overexpression of Interleukin-11 in the Central Nervous System Limits Demyelination and Enhances Remyelination |
| title_sort | local overexpression of interleukin 11 in the central nervous system limits demyelination and enhances remyelination |
| url | http://dx.doi.org/10.1155/2013/685317 |
| work_keys_str_mv | AT anuragmaheshwari localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT krisjanssens localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT jeroenbogie localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT chrisvandenhaute localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT tomstruys localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT ivolambrichts localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT veerlebaekelandt localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT pietstinissen localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT jeromejahendriks localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT helenaslaets localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination AT nielshellings localoverexpressionofinterleukin11inthecentralnervoussystemlimitsdemyelinationandenhancesremyelination |