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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-06-2137. This Article Full Text (PDF) All Versions of this Article: 2003-06-2137v1 103/2/517    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Secchiero, P. Articles by Zauli, G. Search for Related Content PubMed PubMed Citation Articles by Secchiero, P. Articles by Zauli, G. Social Bookmarking                   What's this? Submitted July 8, 2003 Accepted August 28, 2003 TRAIL regulates normal erythroid maturation through an ERK-dependent pathway Paola Secchiero*, Elisabetta Melloni, Markku Heikinheimo, Susanna Mannisto, Roberta Di Pietro, Antonio Iacone, and Giorgio Zauli Department of Morphology and Embryology, Human Anatomy Section, University of Ferrara, Ferrara, Italy Biomedicum Helsinki, Program for Developmental and Reproductive Biology, University of Helsinki, Helsinki, Finland Department of Normal Human Morphology, University of Trieste, Trieste, Italy Department of Transfusion Medicine Study Center, Santo Spirito Hospital of Pescara, Pescara, Italy * Corresponding author; email: secchier{at}mail.umbi.umd.edu. In order to investigate the biological activity of 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 ERK1/2 but not the p38/MAPK or the JNK pathway. Consistently with a key role of ERK1/2 in mediating the negative effects of TRAIL on erythroid maturation, PD98059, a pharmacological inhibitor of the ERK pathway, but not z-VAD-fmk or SB203580, a pharmacological inhibitor of p38/MAPK, reverted the anti-differentiative effect of TRAIL on CB-derived erythroblasts. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Li, Z. Liu, G. Zhuang, P. Yin, H. Tao, J. Qiu, Q. Hu, and J. Zhang Anti-DR5 mAb Ameliorate Adjuvant Arthritis Rats Through Inducing Synovial Cells Apoptosis Experimental Biology and Medicine, December 1, 2009; 234(12): 1468 - 1476. [Abstract] [Full Text] [PDF] C. R. Geest and P. J. Coffer MAPK signaling pathways in the regulation of hematopoiesis J. Leukoc. Biol., August 1, 2009; 86(2): 237 - 250. [Abstract] [Full Text] [PDF] P. Secchiero, F. Corallini, E. Rimondi, C. Chiaruttini, M. G. di Iasio, A. Rustighi, G. Del Sal, and G. Zauli Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells Blood, February 1, 2008; 111(3): 1287 - 1294. [Abstract] [Full Text] [PDF] P. Secchiero, R. Candido, F. Corallini, S. Zacchigna, B. Toffoli, E. Rimondi, B. Fabris, M. Giacca, and G. Zauli Systemic Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Delivery Shows Antiatherosclerotic Activity in Apolipoprotein E-Null Diabetic Mice Circulation, October 3, 2006; 114(14): 1522 - 1530. [Abstract] [Full Text] [PDF] N. Felli, F. Pedini, A. Zeuner, E. Petrucci, U. Testa, C. Conticello, M. Biffoni, A. Di Cataldo, J. A. Winkles, C. Peschle, et al. Multiple Members of the TNF Superfamily Contribute to IFN-{gamma}-Mediated Inhibition of Erythropoiesis J. Immunol., August 1, 2005; 175(3): 1464 - 1472. [Abstract] [Full Text] [PDF] J. Morel, R. Audo, M. Hahne, and B. Combe Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Rheumatoid Arthritis Synovial Fibroblast Proliferation through Mitogen-activated Protein Kinases and Phosphatidylinositol 3-Kinase/Akt J. Biol. Chem., April 22, 2005; 280(16): 15709 - 15718. [Abstract] [Full Text] [PDF] D. Campioni, P. Secchiero, F. Corallini, E. Melloni, S. Capitani, F. Lanza, and G. Zauli Evidence for a Role of TNF-Related Apoptosis-Inducing Ligand (TRAIL) in the Anemia of Myelodysplastic Syndromes Am. J. Pathol., February 1, 2005; 166(2): 557 - 563. [Abstract] [Full Text] [PDF]

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