Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) up-regulated the expression of constitutive cyclooxygenase (COX)-1 protein in HL-60 cells without affecting COX-2. The TRAIL-mediated COX-1 up-regulation was accompanied by a significant increase of the PGE(2) synthesis and release, which was suppressed by the COX-1 inhibitor valeryl salicylate but not by the COX-2 inhibitor NS-398. Experiments carried out by adding exogenous PGE(2) to HL-60 cells indicated that PGE(2) was not involved in TRAIL cytotoxicity and rather showed a dose-dependent protection against TRAIL-induced apoptosis. Importantly, the ability of TRAIL to increase PGE(2) production was also observed in normal, human CD34-derived myeloid cells and in freshly isolated peripheral blood CD14(+) monocytes. Moreover, in contrast to HL-60 cells, primary, normal cells were not susceptible to TRAIL cytotoxicity. These data indicate that the ability of TRAIL to up-regulate eicosanoid production and release is not confined to malignant leukemic cells, but it may also play a role in normal hematopoiesis.
Lingua originale | English |
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pagine (da-a) | 986-994 |
Numero di pagine | 9 |
Rivista | Journal of Leukocyte Biology |
Volume | 72 |
Stato di pubblicazione | Pubblicato - 2002 |
Keywords
- Antigens, CD14
- Antigens, CD34
- Apoptosis Regulatory Proteins
- Caspases
- Cell Lineage
- Cells, Cultured
- Cyclooxygenase 1
- Dinoprostone
- HL-60 Cells
- Humans
- Isoenzymes
- Jurkat Cells
- Kinetics
- Membrane Glycoproteins
- Membrane Proteins
- Monocytes
- Myeloid Cells
- Prostaglandin-Endoperoxide Synthases
- Signal Transduction
- TNF-Related Apoptosis-Inducing Ligand
- Tumor Necrosis Factor-alpha
- Up-Regulation