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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2001-11-0084. This Article Full Text (PDF) All Versions of this Article: 2001-11-0084v1 101/2/524    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 Jacobs-Helber, S. M Articles by Sawyer, S. T Search for Related Content PubMed PubMed Citation Articles by Jacobs-Helber, S. M Articles by Sawyer, S. T Social Bookmarking                   What's this? Submitted November 28, 2001 Accepted August 15, 2002 Tumor necrosis factor- expressed constitutively in erythroid cells or induced by erythropoietin has negative and stimulatory roles in normal erythropoiesis and erythroleukemia Sarah M Jacobs-Helber, Kwan-ho Roh, Daniel Baily, Emmanuel N Dessypris, John J Ryan, Jingchun Chen, Amittha Wickrema, Dwayne L Barber, Paul Dent, and Stephen T Sawyer* Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, USA Department of Biology, Virginia Commonwealth University, Richmond, VA, USA Department of Internal Medicine, Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA, USA Hematology/Oncology Section, University of Chicago, Chicago, IL, USA Division of Cellular and Molecular Biology, Ontario Cancer Institute, Toronto, ON, Canada Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, VA, USA; Department of Radiation Oncology and Physiology, Virginia Commonwealth University, Richmond, VA, USA * Corresponding author; email: ssawyer{at}hsc.vcu.edu. Binding of erythropoietin (EPO) to its receptor (EPOR) on erythroid cells induces the activation of numerous signal transduction pathways, including the mitogen activated protein kinase Jun-N-terminal kinase (JNK). In an effort to understand the regulation of EPO-induced proliferation and JNK activation, we have examined the role of potential autocrine factors in the proliferation of the murine erythroleukemia cell line HCD57. We report here that treatment of these cells with EPO induced the expression and secretion of tumor necrosis factor alpha (TNF-). EPO-dependent proliferation was reduced by the addition of neutralizing antibodies to TNF-, and exogenously added TNF- induced proliferation of HCD57 cells. EPO could also induce TNF- expression in BAF3 and DA3 myeloid cells ectopically expressing the EPOR. Addition of TNF- activated JNK in HCD57 cells, and the activity of JNK was partially inhibited by addition of a TNF- neutralizing antibody. Primary human and murine erythroid progenitors expressed TNF- in either an EPO-dependent or constitutive manner. However, TNF- had an inhibitory effect on both immature primary human and murine cells, suggestive that the proliferative effects of TNF- may be limited to erythroleukemic cells. This study suggests a novel role for autocrine TNF- expression in the proliferation of erythroleukemia cells that is distinct from the effect of TNF- in normal erythropoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Tefferi, S. Verstovsek, G. Barosi, F. Passamonti, G. J. Roboz, H. Gisslinger, R. L. Paquette, F. Cervantes, C. E. Rivera, H. J. Deeg, et al. Pomalidomide Is Active in the Treatment of Anemia Associated With Myelofibrosis J. Clin. Oncol., September 20, 2009; 27(27): 4563 - 4569. [Abstract] [Full Text] [PDF] T. G.P. Bumm, C. Elsea, A. S. Corbin, M. Loriaux, D. Sherbenou, L. Wood, J. Deininger, R. T. Silver, B. J. Druker, and M. W.N. Deininger Characterization of Murine JAK2V617F-Positive Myeloproliferative Disease Cancer Res., December 1, 2006; 66(23): 11156 - 11165. [Abstract] [Full Text] [PDF] H. V. Wright, D. Bailey, M. Kashyap, C. L. Kepley, M. S. Drutskaya, S. A. Nedospasov, and J. J. Ryan IL-3-Mediated TNF Production Is Necessary for Mast Cell Development J. Immunol., February 15, 2006; 176(4): 2114 - 2121. [Abstract] [Full Text] [PDF] Y. Ohene-Abuakwa, K. A. Orfali, C. Marius, and S. E. Ball Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect Blood, January 15, 2005; 105(2): 838 - 846. [Abstract] [Full Text] [PDF] S. M. Jacobs-Helber and S. T. Sawyer Jun N-terminal kinase promotes proliferation of immature erythroid cells and erythropoietin-dependent cell lines Blood, August 1, 2004; 104(3): 696 - 703. [Abstract] [Full Text] [PDF] S. Uddin, J. Ah-Kang, J. Ulaszek, D. Mahmud, and A. Wickrema Differentiation stage-specific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells PNAS, January 6, 2004; 101(1): 147 - 152. [Abstract] [Full Text] [PDF]

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