TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE(2) production in cells of the myeloid lineage.
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.
Secchiero
Paola
P
Department of Morphology and Embryology, Human Anatomy Section, University of Ferrara, Italy.
Gonelli
Arianna
A
Ciabattoni
Giovanni
G
Melloni
Elisabetta
E
Grill
Vittorio
V
Rocca
Bianca
B
Delbello
Giorgio
G
Zauli
Giorgio
G
D018952:Antigens, CD34 / Q000032:analysis; D051017:Apoptosis Regulatory Proteins; D020169:Caspases / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D015232:Dinoprostone / Q000096:biosynthesis*; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008562:Membrane Glycoproteins / Q000494:pharmacology* / Q000633:toxicity; D008565:Membrane Proteins; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D022423:Myeloid Cells / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000633:toxicity; D015854:Up-Regulation
D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; D007527:Isoenzymes; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020169:Caspases; D015232:Dinoprostone