title: Cytokine-induced cell death in human oligodendroglial cell lines. II: Alterations in gene expression induced by interferon-gamma and tumor necrosis factor-alpha.
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.
authors.affiliation: Biomedisch Onderzoeksinstituut, Limburgs Universitair Centrum and School of Life Sciences, Transnationale Universiteit Limburg, Universitaire Campus A, Diepenbeek, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Buntinx
authors.forename: Ellen
authors.initials: E
authors.lastname: Gielen
authors.forename: Paul
authors.initials: P
authors.lastname: Van Hummelen
authors.forename: Jef
authors.initials: J
authors.lastname: Raus
authors.forename: Marcel
authors.initials: M
authors.lastname: Ameloot
authors.forename: Paul
authors.initials: P
authors.lastname: Steels
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5 / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D004357:Drug Synergism; D053222:Fas Ligand Protein; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017304:Annexin A5; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020169:Caspases