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Published on: November 9, 2020
TRAIL induces death of human oligodendrocytes isolated from adult brain
Mariola Matysiak1, Anna Jurewicz, Dariusz Jaskolski
1Department of Neurology, Medical University of Lodz, Poland.
Abstract:
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in various tumour cell lines and, recently, also in normal cells. TRAIL interacts with four receptors: two signalling receptors (TRAIL-R1 and TRAIL-R2) and two decoy receptors (TRAIL-R3 and TRAIL-R4). We have shown that both signalling receptors are present on the surface of oligodendrocytes isolated from adult human brain (ahOL), whereas the decoy receptors are expressed at a low level on ahOL. TRAIL induces ahOL apoptosis--as characterized by Annexin V staining prior to propidium iodide cell uptake--under conditions of protein synthesis inhibition. However, pre-treatment of ahOL with interferon gamma (IFNgamma) evoked susceptibility to TRAIL-induced death, which did not require inhibition of protein synthesis. A blocking experiment with monoclonal antibodies directed against TRAIL-R1 and TRAIL-R2 revealed that TRAIL-R1 is mainly involved in TRAIL-induced apoptosis of ahOL. In contrast to ahOL, microglial cells were completely resistant to cell death induced by TRAIL. Microglial cells had high surface expression of the decoy receptor TRAIL-R3, suggesting that resistance of these glial cells to TRAIL-induced death depends on the presence of the protective effect of TRAIL-R3. Stimulation of microglia with TRAIL increased further expression of TRAIL-R3, but it had no effect on the expression of TRAIL receptors by ahOL. This result may implicate TRAIL as an effector-immune molecule in selective ahOL demise in inflammatory/demyelinating conditions.
Insights
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in human brain oligodendrocytes, particularly when pre-treated with interferon gamma. Microglial cells are resistant due to decoy receptor TRAIL-R3 expression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various cell types.
- TRAIL interacts with signalling receptors (TRAIL-R1, TRAIL-R2) and decoy receptors (TRAIL-R3, TRAIL-R4).
- Oligodendrocytes and microglial cells are key glial cells in the central nervous system.
Purpose of the Study:
- To investigate the role of TRAIL in oligodendrocyte and microglial cell apoptosis.
- To determine the specific TRAIL receptors involved in oligodendrocyte death.
- To elucidate the mechanism of microglial resistance to TRAIL-induced apoptosis.
Main Methods:
- Isolated adult human oligodendrocytes (ahOL) and microglial cells were treated with TRAIL.
- Apoptosis was assessed using Annexin V and propidium iodide staining.
- Blocking experiments with monoclonal antibodies against TRAIL-R1 and TRAIL-R2 were performed.
- Receptor expression levels were analyzed via flow cytometry.
Main Results:
- TRAIL induced apoptosis in ahOL, especially after pre-treatment with interferon gamma (IFNγ).
- TRAIL-R1 was identified as the primary receptor mediating TRAIL-induced ahOL apoptosis.
- Microglial cells exhibited resistance to TRAIL-induced death, correlated with high expression of the decoy receptor TRAIL-R3.
- TRAIL stimulation increased TRAIL-R3 expression in microglia but not in ahOL.
Conclusions:
- TRAIL can induce selective apoptosis in adult human oligodendrocytes, potentially mediated by TRAIL-R1.
- The expression of decoy receptor TRAIL-R3 confers resistance to TRAIL-induced apoptosis in microglial cells.
- TRAIL may function as an immune effector molecule contributing to oligodendrocyte demise in inflammatory and demyelinating conditions.
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