TRAIL regulates normal erythroid maturation through an ERK-dependent pathway

Paola Secchiero, Elisabetta Melloni, Markku Heikinheimo, Susanna Mannisto, Roberta Di Pietro, Antonio Iacone, Giorgio Zauli

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Abstract

In order to investigate the biologic activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on human erythropoiesis, glycophorin A (GPA)+ erythroid cells were generated in serum-free liquid phase from human cord blood (CB) CD34+ progenitor cells. The surface expression of TRAIL-R1 was weakly detectable in the early-intermediate phase of erythroid differentiation (days 4-6; dim-intermediate GPA expression), whereas a clear-cut expression of TRAIL-R2 was observed through the entire course of erythroid differentiation (up to days 12-14; bright GPA expression). On the other hand, surface TRAIL-R3 and -R4 were not detected at any culture time. Besides inducing a rapid but small increase of apoptotic cell death, which was abrogated by the pan-caspase inhibitor z-VAD-fmk, the addition of recombinant TRAIL at day 6 of culture inhibited the generation of morphologically mature erythroblasts. Among the intracellular pathways investigated, TRAIL significantly stimulated the extracellular signal-regulated kinase 1/2 (ERK1/2) but not the p38/mitogen-activated protein kinase (MAPK) or the c-Jun NH 2-terminal kinase (JNK) pathway. Consistently with a key role of ERK1/2 in mediating the negative effects of TRAIL on erythroid maturation, PD98059, a pharmacologic inhibitor of the ERK pathway, but not z-VAD-fmk or SB203580, a pharmacologic inhibitor of p38/MAPK, reverted the antidifferentiative effect of TRAIL on CB-derived erythroblasts.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalBlood
Volume103
Issue number2
DOIs
Publication statusPublished - Jan 15 2004

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Glycophorin
MAP Kinase Signaling System
Erythroblasts
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Fetal Blood
Blood
Erythroid Cells
Caspase Inhibitors
Erythropoiesis
Cell death
Cell Death
Phosphotransferases
Stem Cells
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Liquids
Serum

ASJC Scopus subject areas

  • Hematology

Cite this

Secchiero, P., Melloni, E., Heikinheimo, M., Mannisto, S., Di Pietro, R., Iacone, A., & Zauli, G. (2004). TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. Blood, 103(2), 517-522. https://doi.org/10.1182/blood-2003-06-2137

TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. / Secchiero, Paola; Melloni, Elisabetta; Heikinheimo, Markku; Mannisto, Susanna; Di Pietro, Roberta; Iacone, Antonio; Zauli, Giorgio.

In: Blood, Vol. 103, No. 2, 15.01.2004, p. 517-522.

Research output: Contribution to journalArticle

Secchiero, P, Melloni, E, Heikinheimo, M, Mannisto, S, Di Pietro, R, Iacone, A & Zauli, G 2004, 'TRAIL regulates normal erythroid maturation through an ERK-dependent pathway', Blood, vol. 103, no. 2, pp. 517-522. https://doi.org/10.1182/blood-2003-06-2137
Secchiero P, Melloni E, Heikinheimo M, Mannisto S, Di Pietro R, Iacone A et al. TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. Blood. 2004 Jan 15;103(2):517-522. https://doi.org/10.1182/blood-2003-06-2137
Secchiero, Paola ; Melloni, Elisabetta ; Heikinheimo, Markku ; Mannisto, Susanna ; Di Pietro, Roberta ; Iacone, Antonio ; Zauli, Giorgio. / TRAIL regulates normal erythroid maturation through an ERK-dependent pathway. In: Blood. 2004 ; Vol. 103, No. 2. pp. 517-522.
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