title: 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.
authors: Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.
authors: Ben
authors: B
authors: Emery
authors: Holly S
authors: HS
authors: Cate
authors: Mark
authors: M
authors: Marriott
authors: Tobias
authors: T
authors: Merson
authors: Michele D
authors: MD
authors: Binder
authors: Cameron
authors: C
authors: Snell
authors: Pik Ying
authors: PY
authors: Soo
authors: Simon
authors: S
authors: Murray
authors: Ben
authors: B
authors: Croker
authors: Jian-Guo
authors: JG
authors: Zhang
authors: Warren S
authors: WS
authors: Alexander
authors: Helen
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authors: Cooper
authors: Helmut
authors: H
authors: Butzkueven
authors: Trevor J
authors: TJ
authors: Kilpatrick