Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response.

PloS One
Yifeng LinWensheng Lin

Abstract

Our previous studies have demonstrated that the effects of the immune cytokine interferon-γ (IFN-γ) in immune-mediated demyelinating diseases are mediated, at least in part, by the unfolded protein response (UPR) in oligodendrocytes. Data indicate that some biological effects of IFN-γ are elicited through activation of the transcription factor nuclear factor-κB (NF-κB). Interestingly, it has been shown that activation of the pancreatic endoplasmic reticulum kinase (PERK) branch of the UPR triggers NF-κB activation. In this study, we showed that IFN-γ-induced NF-κB activation was associated with activation of PERK signaling in the oligodendroglial cell line Oli-neu. We further demonstrated that blockage of PERK signaling diminished IFN-γ-induced NF-κB activation in Oli-neu cells. Importantly, we showed that NF-κB activation in oligodendrocytes correlated with activation of PERK signaling in transgenic mice that ectopically express IFN-γ in the central nervous system (CNS), and that enhancing IFN-γ-induced activation of PERK signaling further increased NF-κB activation in oligodendrocytes. Additionally, we showed that suppression of the NF-κB pathway rendered Oli-neu cells susceptible to the cytotoxicity of IFN-γ, reactive oxygen...Continue Reading

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Citations

Aug 27, 2013·Neurotoxicity Research·Pichaya JumnongprakhonJiraporn Tocharus
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Feb 3, 2019·Journal of Neuroinflammation·Yuan YueWensheng Lin
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Aug 28, 2021·International Journal of Molecular Sciences·Kaya E WitteChristian Kaltschmidt

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Methods Mentioned

BETA
Assay
Protein Assay
LightShift
PCR
transgenic

Software Mentioned

Kodak 1D Image Analysis
Sigmastat

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