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Induction of apoptosis in glioma cells by molecules released from activated macrophages
George G Chen1, Ying S Chu, Ernest C W Chak
1Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin. gchen@cuhk.edu.hk
Abstract:
Macrophages play an important role in the regulation of malignant tumors. Although glioma contains abundance of macrophages, their role in apoptosis of glioma is not known. We stimulated macrophages with lipopolysaccharide and culture supernatants of activated macrophages were collected to treat glioma cells. The results showed that molecules released from activated macrophages significantly increased apoptosis of glioma via Fas/FasL and caspase-3 pathways. The level of soluble Fas did not appear to be involved in the mechanism responsible for apoptosis seen in this study, as its level was barely detected in both experimental and control groups. Two cytokines, TNFalpha and IFNgamma, were significantly elevated in the supernatant obtained from the activated macrophages. Considering an important role of these two molecules in the induction of apoptosis mediated by the Fas/FasL system, the present data suggested that TNFalpha and IFNgamma were the main molecules to trigger the cascade of apoptotic reactions in glioma cells. In conclusion, the present study indicates that molecules released from the activated macrophages provide significant signals to stimulate the expression of Fas/FasL and caspase-3, which function to induce apoptosis in glioma cells.
Insights
Activated macrophages release molecules that induce glioma cell death (apoptosis) through Fas/FasL and caspase-3 pathways. Tumor necrosis factor-alpha (TNFα) and interferon-gamma (IFNγ) are key mediators in this process.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Macrophages are crucial in regulating malignant tumors.
- The role of macrophages in glioma apoptosis remains unclear despite their abundance in gliomas.
Purpose of the Study:
- To investigate the effect of activated macrophages on glioma cell apoptosis.
- To identify the molecular mechanisms involved in macrophage-mediated glioma apoptosis.
Main Methods:
- Macrophages were stimulated with lipopolysaccharide.
- Culture supernatants from activated macrophages were used to treat glioma cells.
- Apoptosis pathways (Fas/FasL, caspase-3) and cytokine levels (TNFα, IFNγ) were analyzed.
Main Results:
- Molecules from activated macrophages significantly increased glioma cell apoptosis.
- The Fas/FasL and caspase-3 pathways were implicated in the observed apoptosis.
- Elevated levels of TNFα and IFNγ were detected in activated macrophage supernatants, suggesting their role in initiating apoptosis.
Conclusions:
- Activated macrophages induce glioma cell apoptosis via the Fas/FasL and caspase-3 pathways.
- TNFα and IFNγ are the primary cytokines responsible for triggering apoptosis in glioma cells.
- Macrophage-derived signals are critical for stimulating apoptosis in glioma cells.