Leukaemia inhibitory factor induces an anti-apoptotic response in oligodendrocytes through Akt-phosphorylation and upregulation of 14-3-3

Abstract

Leukaemia inhibitory factor (LIF) promotes the survival of oligodendrocytes (OLG) both in vitro and in an animal model of multiple sclerosis. Here, we show that LIF protects mature rat OLG cultures selectively against the synergistic insult of the proinflammatory cytokines interferon-γ and tumour necrosis factor-α, but it does not protect against oxidative stress nor against staurosporine induced apoptosis. We further demonstrate that LIF activates the janus kinase (Jak)/signal transducer and activator of transcription 3 (STAT3) and the phosphatidylinositol 3 kinase/Akt pathway in mature OLG. We show that LIF protection is independent of suppressors of cytokine signalling and Bcl-2 mRNA expression levels. To gain further insight into the protective mechanism, a quantitative proteomic approach (DIGE) was applied to identify differentially expressed proteins in LIF-treated OLG. Our results indicate that LIF induces a shift in the cellular machinery towards a pro-survival execution program, illustrated by an enhanced expression of isoforms of the anti-apoptotic molecule 14-3-3. These data provide further insight into the mechanisms of LIF-mediated protection of mature oligodendrocytes.

Publication appears at doi: 10.1016/j.jneuroim.2008.04.005