Cytokine‐induced cell death in human oligodendroglial cell lines: I. Synergistic effects of IFN‐γ and TNF‐α on apoptosis

Abstract

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Myelin and oligodendrocytes are considered the major targets of injury caused by a cell-mediated immune response. There is circumstantial evidence that proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) could have disease-promoting roles in multiple sclerosis (MS). In the present study, the cytotoxic effects of IFN-gamma and TNF-alpha on the human oligodendroglial cell lines human oligodendroglioma (HOG) and MO3.13 were analyzed. When the oligodendroglial cell lines were cultured in the presence of IFN-gamma or TNF-alpha, apoptotic cell death was observed in both cell lines after>24 hr incubation. Apoptosis was evidenced by a decrease in cell viability, apoptotic changes in cell and nucleus morphology, and disruption of the membrane asymmetry. Our data show that TNF-alpha and IFN-gamma induce apoptosis in a dose-dependent fashion in both oligodendroglial cell lines and that their synergistic effect results in enhanced cell death. Understanding the regulation of cell death pathways in oligodendrocytes is critical for protecting myelin-producing cells and their associated axons during injury in patients with MS.

Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglioma cell line

“…1A, cell viability was reduced time-dependently to 86.8 ± 5.8%, 56.4 ± 4.3%, and 33.8 ± 0.9%, respectively. As reported previously (8,9), the cytokines acted synergistically to elicit maximal cytotoxic effects. The pattern of cytokine-induced cell death was further confirmed by LDH release assay (Fig.…”

“…The cells were subcultured into either 60 mm dishes (0.8 × 10 6 /2 ml) or 24-well plates (0.3 × 10 5 /0.5 ml/well). After 2 days, the cultures were switched to serum-reduced medium (0.05% FBS) and exposed to the cytokines, TNF-, IFN- (100 ng/ml each), or their combination, in order to induce apoptosis as described previously (9).…”

“…Previous studies, including our own (8,9), aimed at defining the mechanism of cytokine synergy have analyzed changes in intracellular signaling pathways and mediators, but with no clear explanation for the synergistic effects of the cytokines. Hence, we decided to "look outside the cell" with a particular focus on EVs released from cytokineexposed cells.…”

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

“…30 However, during this peak developmental period, preoligodendrocytes are sensitive to reactive oxygen, nitrogen species, and cytokines secreted by microglia. [31][32][33][34][35] Neonatal hypoxia-ischemia and neuroinflammation lead to the activation of astrocytes and microglia, which induces myelin deficiency, associated with long-term cognitive problems. 30,36 Similarly, pain also induces both oxidative stress and inflammatory reactions.…”

A possible role for sPLA2 in oligodendrocyte death and spinal cord injury.

“…Finally Vollgraf, 1998, Mronga et al, 2004), IL-1β (Takahashi et al, 2003), TNFα (Selmaj and Raine, 1988, Buntinx et al, 2004, and AA have all been shown to damage cultured oligodendrocytes.…”