SEARCH:   Advanced

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 Hawiger, J. Articles by Ballard, D. W. Search for Related Content PubMed PubMed Citation Articles by Hawiger, J. Articles by Ballard, D. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 5 (September 1), 1999: pp. 1711-1716 IB Kinase Complex Is an Intracellular Target for Endotoxic Lipopolysaccharide in Human Monocytic Cells Jacek Hawiger, Ruth Ann Veach, Xue-Yan Liu, Sheila Timmons, and Dean W. Ballard From the Department of Microbiology and Immunology and Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN. Endotoxic lipopolysaccharide (LPS) is a proinflammatory agonist produced by gram-negative bacteria and a contributor to the majority of the 400,000 septic shock cases recorded annually in US hospitals. The primary target cells for LPS are monocytes and macrophages. Their response consists of massive production of proinflammatory cytokines, reactive oxygen- and nitrogen-intermediates, procoagulants, and cell adhesion molecules. In turn, expression of these LPS-responsive factors contributes to collapse of the circulatory system, to disseminated intravascular coagulation, and to a 30% mortality rate. A common intracellular mechanism responsible for the expression of septic shock genes in monocytes and macrophages involves the activation of NF-B. This transcription factor is regulated by a family of structurally related inhibitors including IB, IB, and IB, which trap NF-B in the cytoplasm. In this report, the investigators show that LPS derived from different gram-negative bacteria activates cytokine-responsive IB kinases containing catalytic subunits termed IKK (IKK1) and IKK (IKK2). The kinetics of IKK and IKK activation in LPS-stimulated human monocytic cells differ from that recorded on their stimulation with tumor necrosis factor-, thereby implying a distinct activation mechanism. LPS-activated IKK complexes phosphorylate all 3 inhibitors of NF-B: IB, IB, and IB. Moreover, LPS activates IKK preferentially, relative to IKK. Thus, IKK complex constitutes the main intracellular target for LPS-induced NF-B signaling to the nucleus in human monocytic cells to activate genes responsible for septic shock. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Janic, T. M. Umstead, D. S. Phelps, and J. Floros Modulatory effects of ozone on THP-1 cells in response to SP-A stimulation Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L317 - L325. [Abstract] [Full Text] [PDF] T. Syrovets, B. Buchele, C. Krauss, Y. Laumonnier, and T. Simmet Acetyl-Boswellic Acids Inhibit Lipopolysaccharide-Mediated TNF-{alpha} Induction in Monocytes by Direct Interaction with I{kappa}B Kinases J. Immunol., January 1, 2005; 174(1): 498 - 506. [Abstract] [Full Text] [PDF] H. Xiong, H. Li, Y. Chen, J. Zhao, and J. C. Unkeless Interaction of TRAF6 with MAST205 Regulates NF-{kappa}B Activation and MAST205 Stability J. Biol. Chem., October 15, 2004; 279(42): 43675 - 43683. [Abstract] [Full Text] [PDF] J. Sun, F. Li, J. Chen, and J. Xu Effect of Ketamine on NF-kappa B Activity and TNF-alpha Production in Endotoxin-Treated Rats Ann. Clin. Lab. Sci., April 1, 2004; 34(2): 181 - 186. [Abstract] [Full Text] [PDF] P. A. Henriksen, M. Hitt, Z. Xing, J. Wang, C. Haslett, R. A. Riemersma, D. J. Webb, Y. V. Kotelevtsev, and J.-M. Sallenave Adenoviral Gene Delivery of Elafin and Secretory Leukocyte Protease Inhibitor Attenuates NF-{kappa}B-Dependent Inflammatory Responses of Human Endothelial Cells and Macrophages to Atherogenic Stimuli J. Immunol., April 1, 2004; 172(7): 4535 - 4544. [Abstract] [Full Text] [PDF] Y. Takada and B. B. Aggarwal Genetic Deletion of the Tumor Necrosis Factor Receptor p60 or p80 Sensitizes Macrophages to Lipopolysaccharide-induced Nuclear Factor-{kappa}B, Mitogen-activated Protein Kinases, and Apoptosis J. Biol. Chem., June 20, 2003; 278(26): 23390 - 23397. [Abstract] [Full Text] [PDF] S. C. Pingle, J. F. Sanchez, D. M. Hallam, A. L. Williamson, S. B. Maggirwar, and V. Ramkumar Hypertonicity Inhibits Lipopolysaccharide-Induced Nitric Oxide Synthase Expression in Smooth Muscle Cells by Inhibiting Nuclear Factor {kappa}B Mol. Pharmacol., June 1, 2003; 63(6): 1238 - 1247. [Abstract] [Full Text] [PDF] R. S. Carter, K. N. Pennington, B. J. Ungurait, and D. W. Ballard In Vivo Identification of Inducible Phosphoacceptors in the IKK{gamma}/NEMO Subunit of Human I{kappa}B Kinase J. Biol. Chem., May 23, 2003; 278(22): 19642 - 19648. [Abstract] [Full Text] [PDF] S. Kiriakidis, E. Andreakos, C. Monaco, B. Foxwell, M. Feldmann, and E. Paleolog VEGF expression in human macrophages is NF-{kappa}B-dependent: studies using adenoviruses expressing the endogenous NF-{kappa}B inhibitor I{kappa}B{alpha} and a kinase-defective form of the I{kappa}B kinase 2 J. Cell Sci., February 15, 2003; 116(4): 665 - 674. [Abstract] [Full Text] [PDF] M.M. Monick and G.W. Hunninghake Activation of second messenger pathways in alveolar macrophages by endotoxin Eur. Respir. J., July 1, 2002; 20(1): 210 - 222. [Abstract] [Full Text] [PDF] N. Silverman and T. Maniatis NF-{kappa}B signaling pathways in mammalian and insect innate immunity Genes & Dev., September 15, 2001; 15(18): 2321 - 2342. [Full Text] [PDF] D. C. Saha, R. S. Barua, M. E. Astiz, E. C. Rackow, and L-J. Eales-Reynolds Monophosphoryl lipid A stimulated up-regulation of reactive oxygen intermediates in human monocytes in vitro J. Leukoc. Biol., September 1, 2001; 70(3): 381 - 385. [Abstract] [Full Text] [PDF] T. Syrovets, M. Jendrach, A. Rohwedder, A. Schule, and T. Simmet Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKK{beta}-mediated NF-{kappa}B activation Blood, June 15, 2001; 97(12): 3941 - 3950. [Abstract] [Full Text] [PDF] C. Alexander and E. Th. Rietschel Invited review: Bacterial lipopolysaccharides and innate immunity Innate Immunity, June 1, 2001; 7(3): 167 - 202. [Abstract] [PDF] N. H. Purcell, C. Yu, D. He, J. Xiang, N. Paran, J. A. DiDonato, S. Yamaoka, Y. Shaul, and A. Lin Activation of NF-{kappa}B by hepatitis B virus X protein through an I{kappa}B kinase-independent mechanism Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G669 - G677. [Abstract] [Full Text] [PDF] K. Ruckdeschel, O. Mannel, K. Richter, C. A. Jacobi, K. Trulzsch, B. Rouot, and J. Heesemann Yersinia Outer Protein P of Yersinia enterocolitica Simultaneously Blocks the Nuclear Factor-{{kappa}}B Pathway and Exploits Lipopolysaccharide Signaling to Trigger Apoptosis in Macrophages J. Immunol., February 1, 2001; 166(3): 1823 - 1831. [Abstract] [Full Text] [PDF]

	Copyright © 1999 by American Society of Hematology         Online ISSN: 1528-0020