Trail promotes a pro-survival signal in erythropoietin-deprived human erythroblasts through the activation of an NF-κB/IκBα pathway

S. Sancilio, V. Di Giacomo, A. M. Quaglietta, A. Iacone, D. Angelucci, U. Tatasciore, R. A. Rana, A. Cataldi, G. Zauli, Roberta Di Pietro

Research output: Contribution to journalArticlepeer-review

Abstract

The biological activity of TNF-related apoptosis inducing ligand (TRAIL) was analyzed in primary human erythroblasts derived from mononuclear cells of blood donors, kept in culture in the presence of 20% foetal calf serum, growth factors (EPO, SCF, IL-3) and glucocorticoids (10 -6 M dexamethasone, 10 -6 M oestradiol) or under growth factor and serum starvation. In the presence of growth factors and serum, primary erythroblasts showed a differential expression of TRAIL-Receptors (Rs) at various degrees of maturation and responded to TRAIL treatment with a mild cytotoxicity. On the other hand, in the absence of serum and growth factors, TRAIL treatment unexpectedly up-regulated TRAIL-R4 decoy receptor and promoted erythroblast survival. The concomitant activation of NF-κB/IκB survival pathway was detected with Western blotting and immunofluorescence procedures and confirmed by experiments performed with SN50, a pharmacological inhibitor of the NF-κB/IκB pathway. Our study indicates that TRAIL has a twofold activity on erythroid lineages: it induces a mild erythroid cell cytotoxicity in the presence of serum and growth factors, while it promotes erythroid cell survival through the activation of the NF-κB/IκB pathway under starvation conditions.

Original languageEnglish
Pages (from-to)375-386
Number of pages12
JournalJournal of Biological Regulators and Homeostatic Agents
Volume25
Issue number3
Publication statusPublished - Jul 2011

Keywords

  • Erythroblasts
  • NF-κB
  • Starvation
  • Survival
  • TRAIL

ASJC Scopus subject areas

  • Oncology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Immunology and Allergy
  • Immunology
  • Endocrinology
  • Physiology
  • Cancer Research

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