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Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
In this study, the effect of in vitro endotoxin tolerance on
LPS-induced mitogen-activated protein kinase activation, transcription
factor induction, and cytokine, chemokine, and Toll-like receptor (TLR)
2 and 4 gene expression, as well as the involvement of TNF and IL-1
signaling pathways in tolerance, were examined. Pretreatment of mouse
macrophages with LPS inhibited phosphorylation of the extracellular
signal-regulated kinases, c-Jun NH2-terminal kinases, and
p38 kinase; degradation of I-
B
(inhibitory protein that
dissociates from NF-B) and I-Bß; and activation of the
transcription factors NF-B and AP-1 in response to subsequent LPS
stimulation. These changes were accompanied by suppression of
LPS-induced expression of mRNA for GM-CSF, IFN-
-inducible
protein-10, KC, JE/monocyte chemoattractant protein-1,
macrophage-inflammatory protein-1ß, and macrophage-inflammatory
protein-2, with concurrent inhibition of chemokine secretion. In
contrast to control cells, endotoxin-tolerant macrophages exhibited an
increased basal level of TLR2 mRNA, and failed to increase levels of
TLR2 mRNA or to down-regulate TLR4 gene expression upon restimulation
with LPS. As judged by transcription factor activation, LPS and IL-1
were found to induce a state of cross-tolerance against each other,
while no such reciprocal effect was seen for LPS and TNF-. In
addition, macrophages from TNFR I/II double knockout mice were LPS
tolerizable, and blocking of endogenous TNF- with TNFR-Fc fusion
protein did not affect the capacity of LPS to tolerize macrophages.
These data extend our understanding of LPS-signaling mechanisms that
are inhibited in endotoxin-tolerized macrophages and suggest that
endotoxin tolerance might result from impaired expression and/or
functions of common signaling intermediates involved in LPS and IL-1
signaling.
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Y. Tsutsumi-Ishii and I. Nagaoka Modulation of Human {beta}-Defensin-2 Transcription in Pulmonary Epithelial Cells by Lipopolysaccharide-Stimulated Mononuclear Phagocytes Via Proinflammatory Cytokine Production J. Immunol., April 15, 2003; 170(8): 4226 - 4236. [Abstract] [Full Text] [PDF]
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J. D. Schilling, S. M. Martin, D. A. Hunstad, K. P. Patel, M. A. Mulvey, S. S. Justice, R. G. Lorenz, and S. J. Hultgren CD14- and Toll-Like Receptor-Dependent Activation of Bladder Epithelial Cells by Lipopolysaccharide and Type 1 Piliated Escherichia coli Infect. Immun., March 1, 2003; 71(3): 1470 - 1480. [Abstract] [Full Text] [PDF]
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A. E. Medvedev and S. N. Vogel Overexpression of CD14, TLR4, and MD-2 in HEK 293T cells does not prevent induction of in vitro endotoxin tolerance Innate Immunity, February 1, 2003; 9(1): 60 - 64. [Abstract] [PDF]
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 H. Tsujimura, T. Tamura, C. Gongora, J. Aliberti, C. Reis e Sousa, A. Sher, and K. Ozato ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro Blood, February 1, 2003; 101(3): 961 - 969. [Abstract] [Full Text] [PDF]
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S.-J. Yeo, J.-G. Yoon, S.-C. Hong, and A.-K. Yi CpG DNA Induces Self and Cross-Hyporesponsiveness of RAW264.7 Cells in Response to CpG DNA and Lipopolysaccharide: Alterations in IL-1 Receptor-Associated Kinase Expression J. Immunol., January 15, 2003; 170(2): 1052 - 1061. [Abstract] [Full Text] [PDF]
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M. A. Dobrovolskaia, A. E. Medvedev, K. E. Thomas, N. Cuesta, V. Toshchakov, T. Ren, M. J. Cody, S. M. Michalek, N. R. Rice, and S. N. Vogel Induction of In Vitro Reprogramming by Toll-Like Receptor (TLR)2 and TLR4 Agonists in Murine Macrophages: Effects of TLR "Homotolerance" Versus "Heterotolerance" on NF-{kappa}B Signaling Pathway Components J. Immunol., January 1, 2003; 170(1): 508 - 519. [Abstract] [Full Text] [PDF]
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I. Friedrich, J. Spillner, E.-X. Lu, M. Barnscheidt, O. Kuss, A. Sablotzki, F. U. Schade, and J. Borgermann Induction of endotoxin tolerance improves lung function after warm ischemia in dogs Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L224 - L231. [Abstract] [Full Text] [PDF]
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G. Hajishengallis, M. Martin, R. E. Schifferle, and R. J. Genco Counteracting Interactions between Lipopolysaccharide Molecules with Differential Activation of Toll-Like Receptors Infect. Immun., December 1, 2002; 70(12): 6658 - 6664. [Abstract] [Full Text] [PDF]
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A. E. Medvedev, A. Lentschat, L. M. Wahl, D. T. Golenbock, and S. N. Vogel Dysregulation of LPS-Induced Toll-Like Receptor 4-MyD88 Complex Formation and IL-1 Receptor-Associated Kinase 1 Activation in Endotoxin-Tolerant Cells J. Immunol., November 1, 2002; 169(9): 5209 - 5216. [Abstract] [Full Text] [PDF]
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R. D. Erwert, R. K. Winn, J. M. Harlan, and D. D. Bannerman Shiga-like Toxin Inhibition of FLICE-like Inhibitory Protein Expression Sensitizes Endothelial Cells to Bacterial Lipopolysaccharide-induced Apoptosis J. Biol. Chem., October 18, 2002; 277(43): 40567 - 40574. [Abstract] [Full Text] [PDF]
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J. H. Wang, M. Doyle, B. J. Manning, Q. Di Wu, S. Blankson, and H. P. Redmond Induction of Bacterial Lipoprotein Tolerance Is Associated with Suppression of Toll-like Receptor 2 Expression J. Biol. Chem., September 20, 2002; 277(39): 36068 - 36075. [Abstract] [Full Text] [PDF]
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K. Ruckdeschel and K. Richter Lipopolysaccharide Desensitization of Macrophages Provides Protection against Yersinia enterocolitica-Induced Apoptosis Infect. Immun., September 1, 2002; 70(9): 5259 - 5264. [Abstract] [Full Text] [PDF]
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E. A. Kurt-Jones, L. Mandell, C. Whitney, A. Padgett, K. Gosselin, P. E. Newburger, and R. W. Finberg Role of Toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils Blood, August 13, 2002; 100(5): 1860 - 1868. [Abstract] [Full Text] [PDF]
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M. Adib-Conquy and J.-M. Cavaillon Gamma Interferon and Granulocyte/Monocyte Colony-stimulating Factor Prevent Endotoxin Tolerance in Human Monocytes by Promoting Interleukin-1 Receptor-associated Kinase Expression and Its Association to MyD88 and Not by Modulating TLR4 Expression J. Biol. Chem., July 26, 2002; 277(31): 27927 - 27934. [Abstract] [Full Text] [PDF]
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S. Sato, O. Takeuchi, T. Fujita, H. Tomizawa, K. Takeda, and S. Akira A variety of microbial components induce tolerance to lipopolysaccharide by differentially affecting MyD88-dependent and -independent pathways Int. Immunol., July 1, 2002; 14(7): 783 - 791. [Abstract] [Full Text] [PDF]
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R. Jacinto, T. Hartung, C. McCall, and L. Li Lipopolysaccharide- and Lipoteichoic Acid-Induced Tolerance and Cross-Tolerance: Distinct Alterations in IL-1 Receptor-Associated Kinase J. Immunol., June 15, 2002; 168(12): 6136 - 6141. [Abstract] [Full Text] [PDF]
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S. B. Mizel and J. A. Snipes Gram-negative Flagellin-induced Self-tolerance Is Associated with a Block in Interleukin-1 Receptor-associated Kinase Release from Toll-like Receptor 5 J. Biol. Chem., June 14, 2002; 277(25): 22414 - 22420. [Abstract] [Full Text] [PDF]
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J. Fan, A. Kapus, P. A. Marsden, Y. H. Li, G. Oreopoulos, J. C. Marshall, S. Frantz, R. A. Kelly, R. Medzhitov, and O. D. Rotstein Regulation of Toll-Like Receptor 4 Expression in the Lung Following Hemorrhagic Shock and Lipopolysaccharide J. Immunol., May 15, 2002; 168(10): 5252 - 5259. [Abstract] [Full Text] [PDF]
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 T. K. Varma, C. Y. Lin, T. E. Toliver-Kinsky, and E. R. Sherwood Endotoxin-Induced Gamma Interferon Production: Contributing Cell Types and Key Regulatory Factors Clin. Vaccine Immunol., May 1, 2002; 9(3): 530 - 543. [Abstract] [Full Text] [PDF]
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 E. Israel-Assayag and Y. Cormier Adaptation to organic dust exposure: a potential role of l-selectin shedding? Eur. Respir. J., May 1, 2002; 19(5): 833 - 837. [Abstract] [Full Text] [PDF]
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I. Sabroe, E. C. Jones, L. R. Usher, M. K. B. Whyte, and S. K. Dower Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses J. Immunol., May 1, 2002; 168(9): 4701 - 4710. [Abstract] [Full Text] [PDF]
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D. Bosisio, N. Polentarutti, M. Sironi, S. Bernasconi, K. Miyake, G. R. Webb, M. U. Martin, A. Mantovani, and M. Muzio Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma : a molecular basis for priming and synergism with bacterial lipopolysaccharide Blood, May 1, 2002; 99(9): 3427 - 3431. [Abstract] [Full Text] [PDF]
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J. Hu, R. Jacinto, C. McCall, and L. Li Regulation of IL-1 Receptor-Associated Kinases by Lipopolysaccharide J. Immunol., April 15, 2002; 168(8): 3910 - 3914. [Abstract] [Full Text] [PDF]
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A. S. Cross Invited review: Endotoxin tolerance -- current concepts in historical perspective Innate Immunity, April 1, 2002; 8(2): 83 - 98. [PDF]
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G. Sebastiani, V. Blais, V. Sancho, S. N. Vogel, M. M. Stevenson, P. Gros, J.-M. Lapointe, S. Rivest, and D. Malo Host Immune Response to Salmonella enterica Serovar Typhimurium Infection in Mice Derived from Wild Strains Infect. Immun., April 1, 2002; 70(4): 1997 - 2009. [Abstract] [Full Text] [PDF]
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B. K. Yoza, J. Y.-Q. Hu, and C. E. McCall Inhibition of histone deacetylation enhances endotoxin-stimulated transcription but does not reverse endotoxin tolerance Innate Immunity, April 1, 2002; 8(2): 109 - 114. [Abstract] [PDF]
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G. Hajishengallis, M. Martin, H. T. Sojar, A. Sharma, R. E. Schifferle, E. DeNardin, M. W. Russell, and R. J. Genco Dependence of Bacterial Protein Adhesins on Toll-Like Receptors for Proinflammatory Cytokine Induction Clin. Vaccine Immunol., March 1, 2002; 9(2): 403 - 411. [Abstract] [Full Text] [PDF]
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M. W. Hornef, T. Frisan, A. Vandewalle, S. Normark, and A. Richter-Dahlfors Toll-like Receptor 4 Resides in the Golgi Apparatus and Colocalizes with Internalized Lipopolysaccharide in Intestinal Epithelial Cells J. Exp. Med., February 25, 2002; 195(5): 559 - 570. [Abstract] [Full Text] [PDF]
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J. C. Rassa, J. L. Meyers, Y. Zhang, R. Kudaravalli, and S. R. Ross Murine retroviruses activate B cells via interaction with toll-like receptor 4 PNAS, February 19, 2002; 99(4): 2281 - 2286. [Abstract] [Full Text] [PDF]
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M. J. Sweet, C. C. Campbell, D. P. Sester, D. Xu, R. C. McDonald, K. J. Stacey, D. A. Hume, and F. Y. Liew Colony-Stimulating Factor-1 Suppresses Responses to CpG DNA and Expression of Toll-Like Receptor 9 but Enhances Responses to Lipopolysaccharide in Murine Macrophages J. Immunol., January 1, 2002; 168(1): 392 - 399. [Abstract] [Full Text] [PDF]
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M. Ferlito, O. G. Romanenko, S. Ashton, F. Squadrito, P. V. Halushka, and J. A. Cook Effect of cross-tolerance between endotoxin and TNF-{alpha} or IL-1{beta} on cellular signaling and mediator production J. Leukoc. Biol., November 1, 2001; 70(5): 821 - 829. [Abstract] [Full Text] [PDF]
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