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Interferon gamma induces protective non‐canonical signaling pathways in primary neurons
Author(s) -
O'Donnell Lauren A.,
Henkins Kristen M.,
Kulkarni Apurva,
Matullo Christine M.,
Balachandran Siddharth,
Pattisapu Anil K.,
Rall Glenn F.
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13250
Subject(s) - stat1 , signal transduction , microbiology and biotechnology , biology , interferon , mapk/erk pathway , stat protein , staurosporine , immunology , stat3 , protein kinase c
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 γ‐dependent resolution of a neurotropic viral challenge in permissive mice is Stat1‐independent. Here, we show that exogenous IFN γ has no deleterious impact on neuronal viability, and staurosporine‐induced apoptosis in neurons is significantly blunted by the addition of IFN γ, suggesting that IFN γ confers a pro‐survival signal in neurons. To identify the pathways induced by IFN γ in neurons, the activation of alternative signal transducers associated with IFN γ 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 γ addition, implying that the cell‐specific availability of signal transducers can diversify the cellular response following IFN engagement.Interferon gamma (IFNγ) signaling varies depending upon cell type and the inflammatory milieu. In neurons, IFNγ activates extracellular regulated kinase‐1/2 (Erk‐1/2) in the context of low expression of the classical IFNγ signaling molecule Signal Transducers and Activators of Transcription‐1 (STAT1). We propose that such alternative signaling pathways could protect against inflammation, and may be dictated by basal expression of intracellular signal transducers.