Premium
Cytokine‐induced cell death in human oligodendroglial cell lines. II: Alterations in gene expression induced by interferon‐γ and tumor necrosis factor‐α
Author(s) -
Buntinx Mieke,
Gielen Ellen,
Van Hummelen Paul,
Raus Jef,
Ameloot Marcel,
Steels Paul,
Stinissen Piet
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20117
Subject(s) - tumor necrosis factor alpha , cytokine , interferon , tumor necrosis factor α , necrosis , programmed cell death , gene expression , interferon γ , cancer research , gene , biology , cell culture , interferon gamma , immunology , pathology , medicine , apoptosis , genetics
Abstract Cytokines, such as interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α), 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‐α and IFN‐γ 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‐γ. In addition to direct cytotoxic effects, IFN‐γ and TNF‐α 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‐α 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. © 2004 Wiley‐Liss, Inc.