title: Interferon gamma induces protective non-canonical signaling pathways in primary neurons.
abstract: 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, IFNγ-dependent resolution of a neurotropic viral challenge in permissive mice is Stat1-independent. Here, we show that exogenous IFNγ has no deleterious impact on neuronal viability, and staurosporine-induced apoptosis in neurons is significantly blunted by the addition of IFNγ, suggesting that IFNγ confers a pro-survival signal in neurons. To identify the pathways induced by IFNγ in neurons, the activation of alternative signal transducers associated with IFNγ 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 IFNγ addition, implying that the cell-specific availability of signal transducers can diversify the cellular response following IFN engagement.
authors.affiliation: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, USA.|Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: O'Donnell
authors.affiliation: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Henkins
authors.affiliation: Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania, USA.
authors.forename: Apurva
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Matullo
authors.affiliation: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Balachandran
authors.affiliation: Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Pattisapu
authors.affiliation: Fox Chase Cancer Center, Program in Immune Cell Development and Host Defense, Philadelphia, Pennsylvania, USA.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Rall
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D007371:Interferon-gamma / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D000963:Antimetabolites; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D007371:Interferon-gamma; D001973:Bromodeoxyuridine; D019311:Staurosporine
keywords: Erk-1/2; Interferon gamma; Stat1; cytokines; hippocampus; neuron