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CUTTING EDGE |
*
Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118; and
Tularik, South San Francisco, CA 98080
Toll-like receptor (TLR) 2 and TLR4 have been implicated in the responses of cells to LPS (endotoxin). CD14-transfected Chinese hamster ovary (CHO)-K1 fibroblasts (CHO/CD14) are exquisitely sensitive to endotoxin. Sequence analysis of CHO-TLR2, compared with human and mouse TLR2, revealed a single base pair deletion. This frameshift mutation resulted in an alternative stop codon, encoding a protein devoid of transmembrane and intracellular domains. CHO-TLR2 cDNA failed to enable LPS signaling upon transient transfection into human epithelial kidney 293 cells. Site-directed mutagenesis of CHO-TLR2 enabled expression of a presumed full-length hamster TLR2 that conferred LPS responsiveness in human epithelial kidney 293 cells. Genomic TLR2 DNA from primary hamster macrophages also contained the frameshift mutation found in CHO fibroblasts. Nevertheless, hamster peritoneal macrophages were found to respond normally to LPS, as evidenced by the induction of cytokines. These results imply that expression of TLR2 is sufficient but not essential for mammalian responses to endotoxin.
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M. G. Lei and D. C. Morrison Differential Expression of Caveolin-1 in Lipopolysaccharide-Activated Murine Macrophages Infect. Immun., September 1, 2000; 68(9): 5084 - 5089. [Abstract] [Full Text] [PDF]
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N. W. J. Schroder, B. Opitz, N. Lamping, K. S. Michelsen, U. Zahringer, U. B. Gobel, and R. R. Schumann Involvement of Lipopolysaccharide Binding Protein, CD14, and Toll-Like Receptors in the Initiation of Innate Immune Responses by Treponema Glycolipids J. Immunol., September 1, 2000; 165(5): 2683 - 2693. [Abstract] [Full Text] [PDF]
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 L. A. J. O'Neill The Interleukin-1 Receptor/Toll-like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense Sci. Signal., August 8, 2000; 2000(44): re1 - re1. [Abstract] [Full Text] [PDF]
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M. Fujihara, S. Wakamoto, T. Ito, M. Muroi, T. Suzuki, H. Ikeda, and K. Ikebuchi Lipopolysaccharide-triggered desensitization of TNF-{alpha} mRNA expression involves lack of phosphorylation of I{kappa}B{alpha} in a murine macrophage-like cell line, P388D1 J. Leukoc. Biol., August 1, 2000; 68(2): 267 - 276. [Abstract] [Full Text]
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M. Hirschfeld, Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 2 J. Immunol., July 15, 2000; 165(2): 618 - 622. [Abstract] [Full Text] [PDF]
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G. Scholz, K. Cartledge, and A. R. Dunn Hck Enhances the Adherence of Lipopolysaccharide-stimulated Macrophages via Cbl and Phosphatidylinositol 3-Kinase J. Biol. Chem., May 5, 2000; 275(19): 14615 - 14623. [Abstract] [Full Text] [PDF]
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E. Faure, O. Equils, P. A. Sieling, L. Thomas, F. X. Zhang, C. J. Kirschning, N. Polentarutti, M. Muzio, and M. Arditi Bacterial Lipopolysaccharide Activates NF-kappa B through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells. DIFFERENTIAL EXPRESSION OF TLR-4 AND TLR-2 IN ENDOTHELIAL CELLS J. Biol. Chem., April 6, 2000; 275(15): 11058 - 11063. [Abstract] [Full Text] [PDF]
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 J. A. Thomas, R. L. Modlin, H. D. Brightbill, and P. J. Godowski Toll Genes and Responsiveness to Bacterial Endotoxins N. Engl. J. Med., March 2, 2000; 342(9): 664 - 665. [Full Text]
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A. M. Soler-Rodriguez, H. Zhang, H. S. Lichenstein, N. Qureshi, D. W. Niesel, S. E. Crowe, J. W. Peterson, and G. R. Klimpel Neutrophil Activation by Bacterial Lipoprotein Versus Lipopolysaccharide: Differential Requirements for Serum and CD14 J. Immunol., March 1, 2000; 164(5): 2674 - 2683. [Abstract] [Full Text] [PDF]
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T. H. Flo, O. Halaas, E. Lien, L. Ryan, G. Teti, D. T. Golenbock, A. Sundan, and T. Espevik Human Toll-Like Receptor 2 Mediates Monocyte Activation by Listeria monocytogenes, But Not by Group B Streptococci or Lipopolysaccharide J. Immunol., February 15, 2000; 164(4): 2064 - 2069. [Abstract] [Full Text] [PDF]
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T. Matsuguchi, K. Takagi, T. Musikacharoen, and Y. Yoshikai Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes Blood, February 15, 2000; 95(4): 1378 - 1385. [Abstract] [Full Text] [PDF]
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K. Ohashi, V. Burkart, S. Flohe, and H. Kolb Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex J. Immunol., January 15, 2000; 164(2): 558 - 561. [Abstract] [Full Text] [PDF]
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E. Cario, I. M. Rosenberg, S. L. Brandwein, P. L. Beck, H.-C. Reinecker, and D. K. Podolsky Lipopolysaccharide Activates Distinct Signaling Pathways in Intestinal Epithelial Cell Lines Expressing Toll-Like Receptors J. Immunol., January 15, 2000; 164(2): 966 - 972. [Abstract] [Full Text] [PDF]
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A. Kol, A. H. Lichtman, R. W. Finberg, P. Libby, and E. A. Kurt-Jones Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells J. Immunol., January 1, 2000; 164(1): 13 - 17. [Abstract] [Full Text] [PDF]
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T. K. Means, E. Lien, A. Yoshimura, S. Wang, D. T. Golenbock, and M. J. Fenton The CD14 Ligands Lipoarabinomannan and Lipopolysaccharide Differ in Their Requirement for Toll-Like Receptors J. Immunol., December 15, 1999; 163(12): 6748 - 6755. [Abstract] [Full Text] [PDF]
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D. M. Underhill, A. Ozinsky, K. D. Smith, and A. Aderem Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages PNAS, December 7, 1999; 96(25): 14459 - 14463. [Abstract] [Full Text] [PDF]
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E. Lien, T. J. Sellati, A. Yoshimura, T. H. Flo, G. Rawadi, R. W. Finberg, J. D. Carroll, T. Espevik, R. R. Ingalls, J. D. Radolf, et al. Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products J. Biol. Chem., November 19, 1999; 274(47): 33419 - 33425. [Abstract] [Full Text] [PDF]
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A. D. Wright and S. K. Chapes LPS sensitivity in recombinant mice lacking functional alleles at MHCII, Lps and Nramp1 genes Innate Immunity, October 1, 1999; 5(5-6): 297 - 305. [Abstract] [PDF]
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A. Yoshimura, E. Lien, R. R. Ingalls, E. Tuomanen, R. Dziarski, and D. Golenbock Cutting Edge: Recognition of Gram-Positive Bacterial Cell Wall Components by the Innate Immune System Occurs Via Toll-Like Receptor 2 J. Immunol., July 1, 1999; 163(1): 1 - 5. [Abstract] [Full Text] [PDF]
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M. N. Becker, G. Diamond, M. W. Verghese, and S. H. Randell CD14-dependent Lipopolysaccharide-induced beta -Defensin-2 Expression in Human Tracheobronchial Epithelium J. Biol. Chem., September 15, 2000; 275(38): 29731 - 29736. [Abstract] [Full Text] [PDF]
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Y. Lin, H. Lee, A. H. Berg, M. P. Lisanti, L. Shapiro, and P. E. Scherer The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes J. Biol. Chem., August 4, 2000; 275(32): 24255 - 24263. [Abstract] [Full Text] [PDF]
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E. Lien, J. C. Chow, L. D. Hawkins, P. D. McGuinness, K. Miyake, T. Espevik, F. Gusovsky, and D. T. Golenbock A Novel Synthetic Acyclic Lipid A-like Agonist Activates Cells via the Lipopolysaccharide/Toll-like Receptor 4 Signaling Pathway J. Biol. Chem., January 12, 2001; 276(3): 1873 - 1880. [Abstract] [Full Text] [PDF]
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S. Frantz, R. A. Kelly, and T. Bourcier Role of TLR-2 in the Activation of Nuclear Factor kappa B by Oxidative Stress in Cardiac Myocytes J. Biol. Chem., February 9, 2001; 276(7): 5197 - 5203. [Abstract] [Full Text] [PDF]
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B. Opitz, N. W. J. Schroder, I. Spreitzer, K. S. Michelsen, C. J. Kirschning, W. Hallatschek, U. Zahringer, T. Hartung, U. B. Gobel, and R. R. Schumann Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-kappa B Translocation J. Biol. Chem., June 15, 2001; 276(25): 22041 - 22047. [Abstract] [Full Text] [PDF]
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S. Viriyakosol, P. S. Tobias, R. L. Kitchens, and T. N. Kirkland MD-2 Binds to Bacterial Lipopolysaccharide J. Biol. Chem., October 5, 2001; 276(41): 38044 - 38051. [Abstract] [Full Text] [PDF]
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A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, December 5, 2000; 97(25): 13766 - 13771. [Abstract] [Full Text] [PDF]
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