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(Journal of Leukocyte Biology. 2002;72:986-994.)
© 2002 by Society for Leukocyte Biology

TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE₂ production in cells of the myeloid lineage

Paola Secchiero^*, Arianna Gonelli^*, Giovanni Ciabattoni, Elisabetta Melloni^*, Vittorio Grill, Bianca Rocca, Giorgio Delbello and Giorgio Zauli

^* Department of Morphology and Embryology, Human Anatomy Section, University of Ferrara, Italy;
Department of Drug Sciences, "G. D’Annunzio" University of Chieti, Italy;
Department of Human Normal Morphology, University of Trieste, Italy; and
Hemostasis Research Center on Physiopathology of Hemostasis, Department of Histology, Catholic University of Rome, Italy

Correspondence: Giorgio Zauli, M.D., Ph.D., Department of Human Normal Morphology, University of Trieste, Via Manzoni 16, 34138 Trieste, Italy. E-mail: zauli{at}univ.trieste.it

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 PGE₂ 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 PGE₂ to HL-60 cells indicated that PGE₂ was not involved in TRAIL cytotoxicity and rather showed a dose-dependent protection against TRAIL-induced apoptosis. Importantly, the ability of TRAIL to increase PGE₂ 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.

Key Words: hematopoiesis • signal transduction • death receptor • arachidonic acid

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