Role of Arachidonic Acid Metabolites in Effects of TNF-alfa on Proliferation, Viability, Differentiation and Apoptosis of Human Leukaemic Cell Line HL-60
| Authors | |
|---|---|
| Year of publication | 2000 |
| Type | Article in Proceedings |
| Conference | Cells II |
| MU Faculty or unit | |
| Citation | |
| Field | Immunology |
| Description | Tumor necrosis factor-a (TNF-a) has been found to reduce cellular proliferation and viability, and to induce apoptosis, as well as a partial differentiation. These effects could contribute to elimination of leukemic cells. Using human leukemic cell line HL-60 as a model, we administered cyclooxygenase (indomethacin) and lipoxygenase (MK-886) inhibitors together with TNF-a, in order to evaluate the possible role of prostaglandins and leukotrienes in these processes. The following methods were used to assess cell proliferation, differentiation and apoptosis: cells were counted with haemocytometer; apoptosis and cell cycle were quantified using flowcytometry and fluorescence microscopy; viability was detected by means of light microscopy and flowcytometry; differentiation was followed as nonspecific esterase activity. Our results indicate that indomethacin can potentiate TNF-a-induced apoptosis, resulting in the decrease of number of cells and their viability during simultaneous treatment with TNF-a. However, no effect of indomethacin on the TNF-a-induced differentiation was observed. MK-886 reduced proliferation and viability of HL-60 cells and induced their apoptosis. Similar effects were observed when it was administered in combination with TNF-a. MK-886 strongly potentiated differentiation after TNF-a treatment, but did not induce differentiation when administered alone. In conclusion, inhibition of leukotriene production could potentiate differentiation by TNF-a, while prostaglandins could play a negative role in proapoptotic effects of TNF-a. |