期刊
GLIA
卷 58, 期 9, 页码 1082-1093出版社
WILEY
DOI: 10.1002/glia.20989
关键词
oncostatin M; interleukin-27; NF-kappa B; neuroinflammation; neurotoxicity
资金
- National Institutes of Health [NS-57563, NS-50665, T32-NS-48039]
- National Multiple Sclerosis Society [CA1059-A-13, RG 3892]
- China Scholarship Council [2008622086]
Elevated levels of Oncostatin M (OSM), an interleukin-6 family cytokine, have been observed in multiple sclerosis (MS), HIV-associated neurocognitive disorder (HAND), and glioblastoma (GBM); however, its effects within the CNS are not well understood. OSM regulates gene expression primarily by activating the JAK/STAT, NF-kappa B, and/or MAPK pathways, in a cell-type specific manner. In our studies, OSM induces the production of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) from microglia in an NF-kappa B-dependent manner. This expression also partially requires the intermediate production of TNF-alpha and subsequent NF-kappa B activation via TNF-R1. We also demonstrate that OSM-induced TNF-a production from microglia is neurotoxic. The IL-12 family member, IL-27, suppresses OSM-mediated TNF-alpha and iNOS expression at the transcriptional level by inhibiting activation of the NF-kappa B pathway, and rescues the neurotoxicity induced by OSM-stimulated microglia. These studies are the first to demonstrate the proinflammatory effects of OSM in microglia, and also identify IL-27 as a novel inhibitor of inflammatory processes in these cells. (C) 2010 Wiley-Liss, Inc.
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