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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Bureau, F. Articles by Lekeux, P. Search for Related Content PubMed PubMed Citation Articles by Bureau, F. Articles by Lekeux, P. Related Collections Apoptosis Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3683-3691 IMMUNOBIOLOGY Constitutive nuclear factor-B activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins Fabrice Bureau, Alain Vanderplasschen, Fabrice Jaspar, Frédéric Minner, Paul-Pierre Pastoret, Marie-Paule Merville, Vincent Bours, and Pierre Lekeux From the Department of Veterinary Physiology, Department of Parasitic and Infectious Diseases, and Department of Medical Chemistry and Medical Oncology, University of Liège, Belgium. Constitutive nuclear factor kappaB (NF-B) activity protects quiescent mature immune cells from spontaneous apoptosis. Here, we examined whether NF-B exerts its antiapoptotic function in these cells through the control of Bcl-2 family proteins. Specific pharmacologic inhibitors of NF-B were used to achieve total NF-B inactivation in quiescent human blood lymphocytes, granulocytes, and monocytes. NF-B inhibition induced drastic lymphocyte and granulocyte apoptosis, but only moderate monocyte apoptosis. T- and B-cell apoptosis was slow and associated with a gradual down-regulation of the prosurvival Bcl-2 family proteins Bcl-xL and Bcl-2, respectively. By contrast, granulocyte apoptosis was fast and accompanied by a rapid cellular accumulation of Bcl-xS, the proapoptotic Bcl-x isoform that is generated from alternative splicing of the bcl-x pre-mRNA. Finally, antisense bcl-xL and bcl-2 knockdown in T and B cells, respectively, and induction of Bcl-xS expression in granulocytes through antisense oligonucleotide-mediated redirection of bcl-x pre-mRNA splicing were sufficient to induce significant apoptosis in these cells. Taken together, these results reveal that basal NF-B activity preserves homeostasis of quiescent mature lymphocytes and granulocytes through regulation of distinct members of the Bcl-2 family. This study sheds light on the constitutive mechanisms by which NF-B maintains defense integrity. © 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: S. Olivier, P. Close, E. Castermans, L. de Leval, S. Tabruyn, A. Chariot, M. Malaise, M.-P. Merville, V. Bours, and N. Franchimont Raloxifene-Induced Myeloma Cell Apoptosis: A Study of Nuclear Factor-{kappa}B Inhibition and Gene Expression Signature Mol. Pharmacol., May 1, 2006; 69(5): 1615 - 1623. [Abstract] [Full Text] [PDF] C. Desmet, P. Gosset, B. Pajak, D. Cataldo, M. Bentires-Alj, P. Lekeux, and F. Bureau Selective Blockade of NF-{kappa}B Activity in Airway Immune Cells Inhibits the Effector Phase of Experimental Asthma J. Immunol., November 1, 2004; 173(9): 5766 - 5775. [Abstract] [Full Text] [PDF] S. A. McCracken, E. Gallery, and J. M. Morris Pregnancy-Specific Down-Regulation of NF-{kappa}B Expression in T Cells in Humans Is Essential for the Maintenance of the Cytokine Profile Required for Pregnancy Success J. Immunol., April 1, 2004; 172(7): 4583 - 4591. [Abstract] [Full Text] [PDF] S. DELHALLE, A. DUVOIX, M. SCHNEKENBURGER, F. MORCEAU, M. DICATO, and M. DIEDERICH An Introduction to the Molecular Mechanisms of Apoptosis Ann. N.Y. Acad. Sci., December 1, 2003; 1010(1): 1 - 8. [Abstract] [Full Text] [PDF] D. G. Brooks, P. A. Arlen, L. Gao, C. M. R. Kitchen, and J. A. Zack Identification of T cell-signaling pathways that stimulate latent HIV in primary cells PNAS, October 28, 2003; 100(22): 12955 - 12960. [Abstract] [Full Text] [PDF] S. L. Barrans, P. A. S. Evans, S. J. M. O'Connor, S. J. Kendall, R. G. Owen, A. P. Haynes, G. J. Morgan, and A. S. Jack The t(14;18) Is Associated with Germinal Center-derived Diffuse Large B-Cell Lymphoma and Is a Strong Predictor of Outcome Clin. Cancer Res., June 1, 2003; 9(6): 2133 - 2139. [Abstract] [Full Text] [PDF] J. W. Lim, H. Kim, and K. H. Kim Expression of Ku70 and Ku80 Mediated by NF-kappa B and Cyclooxygenase-2 Is Related to Proliferation of Human Gastric Cancer Cells J. Biol. Chem., November 22, 2002; 277(48): 46093 - 46100. [Abstract] [Full Text] [PDF]

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