| First Author | Lin Y | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e36408 |
| PubMed ID | 22574154 | Mgi Jnum | J:187256 |
| Mgi Id | MGI:5435986 | Doi | 10.1371/journal.pone.0036408 |
| Citation | Lin Y, et al. (2012) Interferon-gamma activates nuclear factor-kappa B in oligodendrocytes through a process mediated by the unfolded protein response. PLoS One 7(5):e36408 |
| abstractText | Our previous studies have demonstrated that the effects of the immune cytokine interferon-gamma (IFN-gamma) 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-gamma are elicited through activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Interestingly, it has been shown that activation of the pancreatic endoplasmic reticulum kinase (PERK) branch of the UPR triggers NF-kappaB activation. In this study, we showed that IFN-gamma-induced NF-kappaB 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-gamma-induced NF-kappaB activation in Oli-neu cells. Importantly, we showed that NF-kappaB activation in oligodendrocytes correlated with activation of PERK signaling in transgenic mice that ectopically express IFN-gamma in the central nervous system (CNS), and that enhancing IFN-gamma-induced activation of PERK signaling further increased NF-kappaB activation in oligodendrocytes. Additionally, we showed that suppression of the NF-kappaB pathway rendered Oli-neu cells susceptible to the cytotoxicity of IFN-gamma, reactive oxygen species, and reactive nitrogen species. Our results indicate that the UPR is involved in IFN-gamma-induced NF-kappaB activation in oligodendrocytes and suggest that NF-kappaB activation by IFN-gamma represents one mechanism by which IFN-gamma exerts its effects on oligodendrocytes in immune-mediated demyelinating diseases. |
