Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination
- Author(s)
- Emery, B; Cate, HS; Marriottt, M; Merson, T; Binder, MD; Snell, C; Soo, PY; Murray, S; Croker, B; Zhang, JG; Alexander, WS; Cooper, H; Butzkueven, H; Kilpatrick, TJ;
- Details
- Publication Year 2006-05-16,Volume 103,Issue #20,Page 7859-7864
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- Enhancement of oligodendrocyte survival through activation of leukemia inhibitory factor receptor (LIFR) signaling is a candidate therapeutic strategy for demyelinating disease. However, in other cell types, LIFR signaling is under tight negative regulation by the intracellular protein suppressor of cytokine signaling 3 (SOCS3). We, therefore, postulated that deletion of the SOCS3 gene in oligodendrocytes would promote the beneficial effects of LIFR signaling in limiting demyelination. By studying wild-type and LIF-knockout mice, we established that SOCS3 expression by oligodendrocytes was induced by the demyelinative insult, that this induction depended on LIF, and that enclogenously produced LIF was likely to be a key determinant of the CNS response to oligodendrocyte loss. Compared with wild-type controls, oligo-dendrocyte-specific SOCS3 conditional-knockout mice displayed enhanced c-fos activation and exogenous LIF-induced phosphorylation of signal transducer and activator of transcription 3. Moreover, these SOCS3-deficient mice were protected against cupri-zone-induced oligodendrocyte loss relative to wild-type animals. These results indicate that modulation of SOCS3 expression could facilitate the endogenous response to CNS injury.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- CUPRIZONE-INDUCED DEMYELINATION; CILIARY NEUROTROPHIC FACTOR; IN-VIVO; OLIGODENDROCYTE SURVIVAL; CELL-SURVIVAL; EXPRESSION; PROTEIN; BRAIN; SOCS; REMYELINATION
- Publisher's Version
- https://doi.org/10.1073/pnas.0602574103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-05-16 12:00:00