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Related Collections Hematopoiesis and Stem Cells Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4307-4317 CHEMOKINES Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines Younghee Lee, Akihiko Gotoh, Hyung-Joo Kwon, Minute You, Lisa Kohli, Charlie Mantel, Scott Cooper, Giao Hangoc, Keisuke Miyazawa, Kazuma Ohyashiki, and Hal E. Broxmeyer From the Departments of Microbiology/Immunology, Medicine, Biochemistry and Molecular Biology, and the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis; and First Department of Internal Medicine, Tokyo Medical University, Nishishinjuku, Shinjuku-ku, Tokyo, Japan. Stromal cell-derived factor 1 (SDF-1/CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1 transgenic mice, probably due in part to SDF-1 enhancement of myeloid progenitor cell (MPC) survival. To understand signaling pathways involved in this activity, we studied the effects on factor-dependent cell line MO7e cells incubated with SDF-1 alone or in combination with other cytokines. SDF-1 induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p90RSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p90RSK, and Akt were synergistically activated by SDF-1 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1 followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1. Nuclear factor-B (NF-B) did not appear to be involved in SDF-1 actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1 after delayed addition of growth factors. SDF-1 alone supported survival of highly purified human cord blood CD34+++ cells, less purified human cord blood, and MO7e cells; this effect was synergistically enhanced when SDF-1 was combined with low amounts of other survival-promoting cytokines (GM-CSF, SLF, TPO, and FL). SDF-1 may contribute to maintenance of MPCs in bone marrow by enhancing cell survival alone and in combination with other cytokines. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Xu, E. T. Gonzalez, S. S. Iyer, V. Mac, A. L. Mora, R. L. Sutliff, A. Reed, K. L. Brigham, P. Kelly, and M. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020