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

SUBMITTER: Emery B 

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

REPOSITORIES: biostudies-literature