TNF-related apoptosis-inducing ligand (TRAIL) up-regulates cyclooxygenase (COX)-1 activity and PGE(2) production in cells of the myeloid lineage

P Secchiero, A Gonelli, G Ciabattoni, E Melloni, V Grill, Bianca Rocca, G Delbello, G. Zauli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

16 Citazioni (Scopus)

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 originaleEnglish
pagine (da-a)986-994
Numero di pagine9
RivistaJournal of Leukocyte Biology
Volume72
Stato di pubblicazionePubblicato - 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

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