Research paperMolecular neuroscienceOligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor
Section snippets
Animals
Experiments were conducted in accordance with the National Health and Medical Research Council of Australia guidelines and in accordance with protocols approved by the Howard Florey Institute animal ethics committee. Sprague–Dawley rats were brought from the Australian Research Council (Adelaide, Australia). Every attempt was made to minimize the number of animals required and to minimize their suffering.
Isolation of primary oligodendrocyte progenitor cells
Primary rat oligodendrocyte precursor cells (OPCs) were isolated as previously described (
LIF and IFNγ have opposing effects on oligodendroglial viability
The responsiveness of primary cells to both LIF and INFγ was first confirmed at the level of cell survival. The treatment of cells with LIF resulted in an increase of 41.9% in the proportion of viable cells over a 48-hour period relative to control cultures (P<0.01). In contrast, treatment of cells with IFNγ over this period resulted in a 37.3% decrease in viability (P<0.05). The co-treatment of cells with LIF in addition to IFNγ was sufficient to block this cytotoxic effect of IFNγ, with
Discussion
The present study confirms previous reports that the cytokines LIF and IFNγ have broadly opposing effects on oligodendroglia, with LIF potentiating the survival and IFNγ promoting the death of these cells. Neither the pro-survival activity of LIF nor the pro-death effect of IFNγ predominated when the two cytokines were co-administered: in particular, the administration of LIF rescued IFNγ-treated cultures to near control levels of survival but these cultures still displayed lower viability than
Conclusion
In summary, our findings strongly suggest that the apparently antagonistic effects of LIF and IFNγ upon oligodendrocytes are not subserved by SOCS-mediated negative cross-talk. Instead, the results suggest that the LIF-mediated effect is an independent survival response, given that any potential interactions are downstream of STAT activation. Both cytokines are known to be released during CNS inflammation, with LIF produced by astrocytes (Banner et al., 1997) and IFNγ by infiltrating T cells (
Acknowledgments
This research was supported by the National Health and Medical Research Council of Australia and by The National Multiple Sclerosis Society of the USA.
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