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, Giorgio Zauli

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)986-994
Number of pages9
JournalJournal of Leukocyte Biology
Volume72
Issue number5
Publication statusPublished - Nov 1 2002

Keywords

  • Arachidonic acid
  • Death receptor
  • Hematopoiesis
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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