Unknown

Dataset Information

0

Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination.


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 endogenously produced LIF was likely to be a key determinant of the CNS response to oligodendrocyte loss. Compared with wild-type controls, oligodendrocyte-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 cuprizone-induced oligodendrocyte loss relative to wild-type animals. These results indicate that modulation of SOCS3 expression could facilitate the endogenous response to CNS injury.

SUBMITTER: Emery B 

PROVIDER: S-EPMC1472535 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination.

Emery Ben B   Cate Holly S HS   Marriott Mark M   Merson Tobias T   Binder Michele D MD   Snell Cameron C   Soo Pik Ying PY   Murray Simon S   Croker Ben B   Zhang Jian-Guo JG   Alexander Warren S WS   Cooper Helen H   Butzkueven Helmut H   Kilpatrick Trevor J TJ  

Proceedings of the National Academy of Sciences of the United States of America 20060508 20


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 studyi  ...[more]

Similar Datasets

| S-EPMC5280022 | biostudies-literature
| S-EPMC3370070 | biostudies-literature
| S-EPMC5549259 | biostudies-literature
2023-11-22 | MSV000093466 | MassIVE
| S-EPMC4014316 | biostudies-literature
| S-EPMC3683504 | biostudies-literature
| S-EPMC5512670 | biostudies-literature
| S-EPMC3531439 | biostudies-other
| S-EPMC5861121 | biostudies-literature
| S-EPMC2144613 | biostudies-other