Interferon gamma induces protective non-canonical signaling pathways in primary neurons

摘要

The signal transduction molecule, Stat1, is critical for the expression of type I and II interferon (IFN)-responsive genes in most cells; however, we previously showed that primary hippocampal mouse neurons express low basal Stat1, with delayed and attenuated expression of IFN-responsive genes. Moreover, IFN-dependent resolution of a neurotropic viral challenge in permissive mice is Stat1-independent. Here, we show that exogenous IFN has no deleterious impact on neuronal viability, and staurosporine-induced apoptosis in neurons is significantly blunted by the addition of IFN, suggesting that IFN confers a pro-survival signal in neurons. To identify the pathways induced by IFN in neurons, the activation of alternative signal transducers associated with IFN signaling was assessed. Rapid and pronounced activation of extracellular signal regulated kinase (Erk1/2) was observed in neurons, compared to a modest response in fibroblasts. Moreover, the absence of Stat1 in primary fibroblasts led to enhanced Erk activation following IFN addition, implying that the cell-specific availability of signal transducers can diversify the cellular response following IFN engagement.