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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2351

Title: Cytokine-induced cell death in human oligodendroglial cell lines. II: Alterations in gene expression induced by interferon-gamma and tumor necrosis factor-alpha
Authors: BUNTINX, Mieke
Van Hummelen, P
Issue Date: 2004
Publisher: WILEY-LISS
Citation: JOURNAL OF NEUROSCIENCE RESEARCH, 76(6). p. 846-861
Abstract: Cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), can initiate dual effects resulting in either cell growth or cell death. In this study, the human oligodendroglial cell lines HOG and MO3.13 were used as a model to study the molecular mechanisms of cytokine-induced cell death in human oligodendrocytes. We have previously shown that TNF-alpha and IFN-gamma induce apoptosis in both oligodendroglial cell lines within 72 hr. In the present study, the cell death pathways operating within these cells were further investigated at the gene expression level. Both cell lines express a broad repertoire of caspases and apoptosis-related genes. Some of these genes are specifically up-regulated by cytokine treatment; e.g., caspase-1 is up-regulated by IFN-gamma. In addition to direct cytotoxic effects, IFN-gamma and TNF-alpha also enhance the expression of Fas, TNFR1, and MHC class I molecules in both cell lines. This suggests that cytokines can make oligodendrocytes more vulnerable to different cell death pathways in an inflammatory environment. cDNA microarray analysis of the HOG cell line revealed that TNF-alpha induces genes that regulate apoptosis, survival, inflammation, cell metabolism, and cell signaling. The data suggest that oligodendroglial cells activate both death and survival pathways upon cytokine challenges. However, the survival pathways seem to be unable to compete with the death signal after more than 24 hr of cytokine treatment. These results may contribute to the development of therapeutic strategies aimed at interfering with cytokine-induced cell death of oligodendrocytes in patients with multiple sclerosis. (C) 2004 Wiley-Liss, Inc.
Notes: Limburgs Univ Ctr, Sch Life Sci, Transit Univ Limburg, Biomed Onderzoeksinst, B-3590 Diepenbeek, Belgium. Flemish Interuniv Inst Biotechnol, MicroArray Facil, Louvain, Belgium.Stinissen, P, Limburgs Univ Ctr, Sch Life Sci, Transit Univ Limburg, Biomed Onderzoeksinst, Univ Campus A, B-3590 Diepenbeek, Belgium.piet.stinissen@luc.ac.be
URI: http://hdl.handle.net/1942/2351
DOI: 10.1002/jnr.20117
ISI #: 000221836200010
ISSN: 0360-4012
Category: A1
Type: Journal Contribution
Validation: ecoom, 2005
Appears in Collections: Research publications

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