Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response.
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 t...
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Public Library of Science (PLoS)
2012-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3344863?pdf=render |
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author | Yifeng Lin Stephanie Jamison Wensheng Lin |
author_facet | Yifeng Lin Stephanie Jamison Wensheng Lin |
author_sort | Yifeng Lin |
collection | DOAJ |
description | 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 species, and reactive nitrogen species. Our results indicate that the UPR is involved in IFN-γ-induced NF-κB activation in oligodendrocytes and suggest that NF-κB activation by IFN-γ represents one mechanism by which IFN-γ exerts its effects on oligodendrocytes in immune-mediated demyelinating diseases. |
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spelling | doaj.art-a76197b566f048f397c4b6cc6161a3ae2022-12-22T02:46:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3640810.1371/journal.pone.0036408Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response.Yifeng LinStephanie JamisonWensheng LinOur 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 species, and reactive nitrogen species. Our results indicate that the UPR is involved in IFN-γ-induced NF-κB activation in oligodendrocytes and suggest that NF-κB activation by IFN-γ represents one mechanism by which IFN-γ exerts its effects on oligodendrocytes in immune-mediated demyelinating diseases.http://europepmc.org/articles/PMC3344863?pdf=render |
spellingShingle | Yifeng Lin Stephanie Jamison Wensheng Lin Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. PLoS ONE |
title | Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. |
title_full | Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. |
title_fullStr | Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. |
title_full_unstemmed | Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. |
title_short | Interferon-γ activates nuclear factor-κ B in oligodendrocytes through a process mediated by the unfolded protein response. |
title_sort | interferon γ activates nuclear factor κ b in oligodendrocytes through a process mediated by the unfolded protein response |
url | http://europepmc.org/articles/PMC3344863?pdf=render |
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