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*
Department of Host Defense, Research Institute for Microbial Diseases and
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Osaka University, Osaka, Japan;
Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan; and
¶ Immunobiology Research Group, Gesellschaft für Biotechnologische Forsechung, Braunscheweig, Germany
Bacterial lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor (TLR) 4, a member of the TLR family that participates in pathogen recognition. TLRs recruit a cytoplasmic protein, MyD88, upon pathogen recognition, mediating its function for immune responses. Two major pathways for LPS have been suggested in recent studies, which are referred to as MyD88-dependent and -independent pathways. We report in this study the characterization of the MyD88-independent pathway via TLR4. MyD88-deficient cells failed to produce inflammatory cytokines in response to LPS, whereas they responded to LPS by activating IFN-regulatory factor 3 as well as inducing the genes containing IFN-stimulated regulatory elements such as IP-10. In contrast, a lipopeptide that activates TLR2 had no ability to activate IFN-regulatory factor 3. The MyD88-independent pathway was also activated in cells lacking both MyD88 and TNFR-associated factor 6. Thus, TLR4 signaling is composed of at least two distinct pathways, a MyD88-dependent pathway that is critical to the induction of inflammatory cytokines and a MyD88/TNFR-associated factor 6-independent pathway that regulates induction of IP-10.
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 W. Kozak, S. Wrotek, and A. Kozak Pyrogenicity of CpG-DNA in mice: role of interleukin-6, cyclooxygenases, and nuclear factor-{kappa}B Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R871 - R880. [Abstract] [Full Text] [PDF]
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 Y.-T.A. Teng Protective and Destructive Immunity in the Periodontium: Part 1--Innate and Humoral Immunity and the Periodontium Journal of Dental Research, March 1, 2006; 85(3): 198 - 208. [Abstract] [Full Text] [PDF]
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Y.-T.A. Teng Protective and Destructive Immunity in the Periodontium: Part 2--T-cell-mediated Immunity in the Periodontium Journal of Dental Research, March 1, 2006; 85(3): 209 - 219. [Abstract] [Full Text] [PDF]
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 K. Yang, H. Shi, R. Qi, S. Sun, Y. Tang, B. Zhang, and C. Wang Hsp90 Regulates Activation of Interferon Regulatory Factor 3 and TBK-1 Stabilization in Sendai Virus-infected Cells Mol. Biol. Cell, March 1, 2006; 17(3): 1461 - 1471. [Abstract] [Full Text] [PDF]
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S. K. Biswas, L. Gangi, S. Paul, T. Schioppa, A. Saccani, M. Sironi, B. Bottazzi, A. Doni, B. Vincenzo, F. Pasqualini, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-{kappa}B and enhanced IRF-3/STAT1 activation) Blood, March 1, 2006; 107(5): 2112 - 2122. [Abstract] [Full Text] [PDF]
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 S. Chanchevalap, M. O. Nandan, B. B. McConnell, L. Charrier, D. Merlin, J. P. Katz, and V. W. Yang Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells Nucleic Acids Res., February 25, 2006; 34(4): 1216 - 1223. [Abstract] [Full Text] [PDF]
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M. Sanchez-Alavez, I. V. Tabarean, M. M. Behrens, and T. Bartfai Ceramide mediates the rapid phase of febrile response to IL-1beta PNAS, February 21, 2006; 103(8): 2904 - 2908. [Abstract] [Full Text] [PDF]
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J. S. Campbell, K. J. Riehle, J. T. Brooling, R. L. Bauer, C. Mitchell, and N. Fausto Proinflammatory Cytokine Production in Liver Regeneration Is Myd88-Dependent, but Independent of Cd14, Tlr2, and Tlr4 J. Immunol., February 15, 2006; 176(4): 2522 - 2528. [Abstract] [Full Text] [PDF]
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T. Mahieu, J. M. Park, H. Revets, B. Pasche, A. Lengeling, J. Staelens, A. Wullaert, I. Vanlaere, T. Hochepied, F. van Roy, et al. The wild-derived inbred mouse strain SPRET/Ei is resistant to LPS and defective in IFN-beta production PNAS, February 14, 2006; 103(7): 2292 - 2297. [Abstract] [Full Text] [PDF]
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S. H. Han, J. H. Kim, H. S. Seo, M. H. Martin, G.-H. Chung, S. M. Michalek, and M. H. Nahm Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak2 J. Immunol., January 1, 2006; 176(1): 573 - 579. [Abstract] [Full Text] [PDF]
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R. Mashima, K. Saeki, D. Aki, Y. Minoda, H. Takaki, T. Sanada, T. Kobayashi, H. Aburatani, Y. Yamanashi, and A. Yoshimura FLN29, a Novel Interferon- and LPS-inducible Gene Acting as a Negative Regulator of Toll-like Receptor Signaling J. Biol. Chem., December 16, 2005; 280(50): 41289 - 41297. [Abstract] [Full Text] [PDF]
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H. Yumoto, H.-H. Chou, Y. Takahashi, M. Davey, F. C. Gibson III, and C. A. Genco Sensitization of Human Aortic Endothelial Cells to Lipopolysaccharide via Regulation of Toll-Like Receptor 4 by Bacterial Fimbria-Dependent Invasion Infect. Immun., December 1, 2005; 73(12): 8050 - 8059. [Abstract] [Full Text] [PDF]
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Z. Guo, S. Garg, K. M. Hill, L. Jayashankar, M. R. Mooney, M. Hoelscher, J. M. Katz, J. M. Boss, and S. Sambhara A Distal Regulatory Region Is Required for Constitutive and IFN-{beta}-Induced Expression of Murine TLR9 Gene J. Immunol., December 1, 2005; 175(11): 7407 - 7418. [Abstract] [Full Text] [PDF]
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M. Svensson, S. Zubairi, A. Maroof, F. Kazi, M. Taniguchi, and P. M. Kaye Invariant NKT Cells Are Essential for the Regulation of Hepatic CXCL10 Gene Expression during Leishmania donovani Infection Infect. Immun., November 1, 2005; 73(11): 7541 - 7547. [Abstract] [Full Text] [PDF]
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C. W. Wieland, S. Florquin, N. A. Maris, K. Hoebe, B. Beutler, K. Takeda, S. Akira, and T. van der Poll The MyD88-Dependent, but Not the MyD88-Independent, Pathway of TLR4 Signaling Is Important in Clearing Nontypeable Haemophilus influenzae from the Mouse Lung J. Immunol., November 1, 2005; 175(9): 6042 - 6049. [Abstract] [Full Text] [PDF]
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P. Mandal, M. Novotny, and T. A. Hamilton Lipopolysaccharide Induces Formyl Peptide Receptor 1 Gene Expression in Macrophages and Neutrophils via Transcriptional and Posttranscriptional Mechanisms J. Immunol., November 1, 2005; 175(9): 6085 - 6091. [Abstract] [Full Text] [PDF]
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K. Honda, H. Yanai, A. Takaoka, and T. Taniguchi Regulation of the type I IFN induction: a current view Int. Immunol., November 1, 2005; 17(11): 1367 - 1378. [Abstract] [Full Text] [PDF]
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H. Qin, C. A. Wilson, S. J. Lee, X. Zhao, and E. N. Benveniste LPS induces CD40 gene expression through the activation of NF-{kappa}B and STAT-1{alpha} in macrophages and microglia Blood, November 1, 2005; 106(9): 3114 - 3122. [Abstract] [Full Text] [PDF]
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 K. Fuse, G. Chan, Y. Liu, P. Gudgeon, M. Husain, M. Chen, W.-C. Yeh, S. Akira, and P. P. Liu Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3-Induced Myocarditis and Influences Type I Interferon Production Circulation, October 11, 2005; 112(15): 2276 - 2285. [Abstract] [Full Text] [PDF]
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S. Shi, A. Blumenthal, C. M. Hickey, S. Gandotra, D. Levy, and S. Ehrt Expression of Many Immunologically Important Genes in Mycobacterium tuberculosis-Infected Macrophages Is Independent of Both TLR2 and TLR4 but Dependent on IFN-{alpha}{beta} Receptor and STAT1 J. Immunol., September 1, 2005; 175(5): 3318 - 3328. [Abstract] [Full Text] [PDF]
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M. B. Drennan, B. Stijlemans, J. Van Den Abbeele, V. J. Quesniaux, M. Barkhuizen, F. Brombacher, P. De Baetselier, B. Ryffel, and S. Magez The Induction of a Type 1 Immune Response following a Trypanosoma brucei Infection Is MyD88 Dependent J. Immunol., August 15, 2005; 175(4): 2501 - 2509. [Abstract] [Full Text] [PDF]
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H. Shindou, S. Ishii, M. Yamamoto, K. Takeda, S. Akira, and T. Shimizu Priming Effect of Lipopolysaccharide on Acetyl-Coenzyme A:Lyso-Platelet-Activating Factor Acetyltransferase Is MyD88 and TRIF Independent J. Immunol., July 15, 2005; 175(2): 1177 - 1183. [Abstract] [Full Text] [PDF]
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U. M. Nagarajan, D. M. Ojcius, L. Stahl, R. G. Rank, and T. Darville Chlamydia trachomatis Induces Expression of IFN-{gamma}-Inducible Protein 10 and IFN-{beta} Independent of TLR2 and TLR4, but Largely Dependent on MyD88 J. Immunol., July 1, 2005; 175(1): 450 - 460. [Abstract] [Full Text] [PDF]
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V. U. Toshchakov, S. Basu, M. J. Fenton, and S. N. Vogel Differential Involvement of BB Loops of Toll-IL-1 Resistance (TIR) Domain-Containing Adapter Proteins in TLR4- versus TLR2-Mediated Signal Transduction J. Immunol., July 1, 2005; 175(1): 494 - 500. [Abstract] [Full Text] [PDF]
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G. Gautier, M. Humbert, F. Deauvieau, M. Scuiller, J. Hiscott, E. E.M. Bates, G. Trinchieri, C. Caux, and P. Garrone A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells J. Exp. Med., May 2, 2005; 201(9): 1435 - 1446. [Abstract] [Full Text] [PDF]
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S. M. Zughaier, S. M. Zimmer, A. Datta, R. W. Carlson, and D. S. Stephens Differential Induction of the Toll-Like Receptor 4-MyD88-Dependent and -Independent Signaling Pathways by Endotoxins Infect. Immun., May 1, 2005; 73(5): 2940 - 2950. [Abstract] [Full Text] [PDF]
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A. Schoenemeyer, B. J. Barnes, Margo. E. Mancl, E. Latz, N. Goutagny, P. M. Pitha, K. A. Fitzgerald, and D. T. Golenbock The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling J. Biol. Chem., April 29, 2005; 280(17): 17005 - 17012. [Abstract] [Full Text] [PDF]
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