Recognition of Lipopolysaccharide by The Toll Receptor Complex

• Project/Area Number: 12470078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo (2001-2002); 佐賀医科大学 (2000)
• Principal Investigator: MIYAKE Kensuke The Institute of Medical Science, professor, 医科学研究所, 教授 (60229812)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥16,300,000 (Direct Cost: ¥16,300,000); Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2000: ¥8,700,000 (Direct Cost: ¥8,700,000)
• Keywords: innate immunity / Toll-like receptor / MD-2 / Lipopolysaccharide / pathogen / RP105 / MD-1 / LPS

Research Abstract

LPS is a principal component of Gram-negative bacteria that activates the innate immune system, and one of the best-studied microbial products. LPS recognition molecules are MD-2 and Toll-like receptor 4 (TLR4). MD-2 is indispensable for LPS responses, since mice lacking MD-2 do not respond to LPS.

Research Products

• [Publications] Koarada, S.: "B cells lacking RP105, a novel B cell antigen, in systemic lupus erythematosus"Arthritis Rheum.. 42. 2593-2600 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yashiro-Ohtani, Y.: "Non-CD28 costimulatory molecules present in T cell rafts induce T cell costimulation by enhancing the association of T cell receptor with rafts"J. Immunol.. 164. 1251-1259 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawasaki, K.: "Mouse TLR4-MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol"J. Biol. Chem.. 275. 2251-2254 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akashi, S.: "Regulatory roles for CD14 and phosphatidylinositol in the signaling via Toll-like Receptor 4-MD-2"Res. Commu.. 268. 172-177 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Akashi, S.: "Cutting Edge : Cell surface expression and LPS signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages"J. Immunol.. 164. 3471-3475 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nomura, F.: "Cutting Edge : Endotoxin tolerance in mouse peritoneal macrophages correlates with downregulation of surface TLR4 expression"J. Immunol.. 164. 3476-3479 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogata, H.: "The Toll-like Receptor Protein RP105 Regulates Lipopolysaccharide Signaling in B Cells"J. Exp. Med.. 192. 23-29 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tabeta, K.: "Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts"Infect. Immun.. 68. 3731-3735 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Thoma-Uszynski, S.: "Activation of Toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10"J. Immunol.. 165. 3804-3810 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukuoka, M.: "Antiadhesive function of 130-kd glycoform of CD43 expressed in CD4 T-lymphocyte clones and transfectant cell lines"Blood. 96. 4267-4275 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Dziarski, R.: "MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components"J. Immunol.. 166. 1938-1944 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kaji, K.: "Functional association of CD9 with the Fcγ receptors in macrophages"J. Immunol.. 166. 3256-3265 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yang, S.: "Micrococcus luteus Teichuronic Acids Activate Human and Murine Monocytic Cells in a CD14-and Toll-Like Receptor4-Dependent Manner"Infect. Immun.. 69. 2025-2030 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Watanabe, Y.: "Differentiation stages of eosinophils characterized by hyaluronic acid binding via CD44 and responsiveness to stimuli"DNA Cell Biol.. 20. 189-202 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagai, Y.: "Requirement for MD-1 in Cell Surface Expression of RP105/CD180 and B Cell Responsiveness to Lipopolysaccharide"Blood. 99. 1699-1705 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"nat. immunol.. 3. 667-672 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Matsumoto, M.: "Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling"Biochem. Biophys. Res. Commu.. 293. 1364-1369 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Duesberg U: "Cell activation by synthetic lipopeptides of the hepatitis C virus (HCV)-core protein is mediated by toll like receptors (TLRs) 2 and 4"Immunol Lett. 84. 89-95 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Termeer, C.: "Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4"J. Exp. Med.. 195. 99-111 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Bosisio D.: "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. 99. 3427-3431 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Abel B.: "Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice"J. Immunol.. 169. 3155-3162 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ogawa, T.: "Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4-and myeloid differentiation factor 88-dependent signaling pathway"Int Immunol.. 11. 1325-1332 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hijiya, N.: "Possible involvement of toll-like receptor 4 in endothelial cell activation of larger vessels in response to lipopolysaccharide"Pathobiology. 70. 18-25 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takada, H.: "Saccharomyces cerevisiae-and Candida albicans-Derived Mannan Induced Production of Tumor Necrosis Factor Alpha by Human Monocytes in a CD14-and Toll-Like Receptor 4-Dependent Manner"Microbiol. Immunol.. 46. 503-512 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Miyake, K.: "Essential role of MD-2 in B-cell responses to lipopolysaccharide and Toll-like receptor 4 distribution"J. Endotoxin Rec.. 8. 449-452 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Miyake, K.: "Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2 : unique roles for MD-2"Int Immunopharmacol.. 1. 119-128 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Koarada, S.: "B cells lacking RP105, a novel B cell antigen, in systemic lupus erythematosus"Arthritis Rheum.. 42. 2593-2600 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yashiro-Ohtani, Y.: "Non-CD28 costimulatory molecules present in T cell rafts induce T cell costimulation by enhancing the association of T cell receptor with rafts"J. Immunol.. 164. 1251-1259 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kawasaki, K.: "Mouse TLR4-MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol"J. Biol. Chem.. 275. 2251-2254 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akashi, S.: "Regulatory roles for CD14 and phosphatidylinositol in the signaling via Toll-like Receptor 4-MD-2"Res. Commu.. 268. 172-177 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akashi, S.: "Cutting Edge : Cell surface expression and LPS signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages"J. Immunol.. 164. 3471-3475 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nomura, F.: "Cutting Edge : Endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface TLR4 expression"J. Immunol.. 164. 3476-3479 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ogata, H.: "The Toll-like Receptor Protein RP105 Regulates Lipopolysaccharide Signaling in B Cells"J. Exp. Med.. 192. 23-29 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tabeta, K.: "Toll-like receptors confer responsiveness to lipopolysaccliaride from Porphyromonas gingivalis in human gingival fibroblasts"Infect. Immun.. 68. 3731-3735 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Thoma-Uszynski, S.: "Activation of Toll-like receptor 2 on human dendritic cells triggers induction of IL-12, but not IL-10"J. Immunol.. 165. 3804-3810 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fukuoka, M.: "Antiadhesive function of 130-kd glycoform of CD43 expressed in CD4 T-lymphocyte clones and transfectant cell lines"Blood.. 96. 4267-4275 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Dziarski, R.: "MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components"J. Immunol.. 166. 1938-1944 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kaji, K.: "Functional association of CD9 with the Fcγ receptors in macrophages"J. Immunol.. 166. 3256-3265 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yang, S.: "Micrococcus luteus Teichuronic Acids Activate Human and Murine Monocytic Cells in a CD14-and Toll-Like Receptor4-Dependent Manner"Infect. Immun.. 69. 2025-2030 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Watanabe, Y.: "Differentiation stages of eosinophils characterized by hyaluronic acid binding via CD44 and responsiveness to stimuli"DNA Cell Biol.. 20. 189-202 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagai, Y.: "Requirement for MD-1 in Cell Surface Expression of RP105/CD180 and B Cell Responsiveness to Lipopolysaccharide"Blood.. 99. 1699-1705 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagai, Y.: "Essential role of MD-2 in LPS responsiveness and TLR4 distribution"nat.immunol.. 3. 667-672 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Matsumoto, M.: "Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling"Biochem. Biophys. Res. Commu.. 293. 1364-1369 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Duesberg, U.: "Cell activation by synthetic lipopeptides of the hepatitis C virus (HCV)-core protein is mediated by toll like receptors (TLRs) 2 and 4"Immunol Lett. 84. 89-95 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Termeer, C.: "Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4"J. Exp. Med.. 195. 99-111 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Bosisio D.: "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. 99. 3427-3431 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Abel B.: "Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice"J. Immunol.. 169. 3155-3162 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ogawa, T.: "Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88-dependent signaling pathway"Int Immunol.. 11. 1325-1332 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hijiya, N.: "Possible involvement of toll-like receptor 4 in endothelial cell activation of larger vessels in response to lipopolysaccharide"Pathobiology. 70. 18-25 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takada, H.: "Saccharomyces cerevisiae-and Candida albicans-Derived Mannan Induced Production of Tumor Necrosis Factor Alpha by Human Monocytes in a CD14-and Toll-Like Receptor 4-Dependent Manner"Microbiol. Immunol.. 46. 503-512 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyake, K.: "Essential role of MD-2 in B-cell responses to lipopolysaccharide and Toll-like receptor 4 distribution"J.Endotoxin Rec.. 8. 449-452 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Miyake, K.: "Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2 : unique roles for MD-2"Int Immunopharmacol.. 3. 119-128 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Termeer, C.: "Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4."J. Exp. Med.. 195. 99-111 (2002)
• [Publications] Nagai, Y.: "Requirement for MD-1 in Cell Surface Expression of RP105/CD180 and B Cell Responsiveness to Lipopolysaccharide"Blood. 99. 1699-1705 (2002)
• [Publications] Bosisio D.: "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. 99. 3427-3431 (2002)
• [Publications] Nagai, Y.: "Essential role of MD-1 in lipopolysaccharide responsiveness and Toll-like receptor 4 distribution"Nat. Immunol.. 3. 667-672 (2002)
• [Publications] Matsumoto, M.: "Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling"Biochem. Biophys. Res. Commu.. 293. 1364-1369 (2002)
• [Publications] Abel B.: "Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice"J. Immunol.. 169. 3155-3162 (2002)
• [Publications] Ogawa, T.: "Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4-and myeloid differentiation factor 88-dependent signaling pathway"Int. Immunol.. 11. 1325-1332 (2002)
• [Publications] Hijiya, N.: "Possible involvement of toll-like receptor 4 in endothelial cell activation of larger vessels in response to lipopolysaccharide"Pathobiology. 70. 18-25 (2002)
• [Publications] Miyake, K.: "Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2:unique roles for MD-2"Int Immunopharmacol.. 1. 119-128 (2003)
• [Publications] Kaji, K.: "Functional association of CD9 with the Fcg receptors in macrophages"J.Immunol.. 166. 3256-3265 (2001)
• [Publications] Watanabe, Y.: "Differentiation stages of eosinophils characterized by hyaluronic acid binding via CD44 and responsiveness to stimuli"DNA Cell Biol.. 20. 189-202 (2001)
• [Publications] Schromm, A.: "Molecular genetic analysis of an endotoxin nonresponder mutant cell line : a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling"J.Exp.Med.. 194. 79-88 (2001)
• [Publications] Akashi, S.: "Human MD-2 Confers on Mouse Toll-like Receptor 4 Species-specific LPS Recognition"Int.Immunol.. 13. 1595-1599 (2001)
• [Publications] Nagai, Y.: "Requirement for MD-1 in Cell Surface Expression of RP105/CD180 and B Cell Responsiveness to Lipopolysaccharide"Blood. 99.5. 1699-1705 (2002)
• [Publications] Hayashi,S.-I.: "The CD9 molecule on stromal cells."Leukemia and Lymphoma. 38. 265-270 (2000)
• [Publications] Ogata,H.: "The Toll-like Receptor Protein RP105 Regulates Lipopolysaccharide Signaling in B Cells."J.Exp.Med.. 192. 23-30 (2000)
• [Publications] Tabeta,K.: "Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts."Infect.Immun.. 68. 3731-3735 (2000)
• [Publications] Sugawara,S.: "Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness."J.Immunol.. 165. 411-418 (2000)
• [Publications] Jiang,Q.: "Lipopolysaccharide Induces Physical Proximity Between CD14 and Toll-like Receptor 4 (TLR4) Prior to Nuclear Translocation of NF-B."J.Immunol.. 165. 3541-3544 (2000)
• [Publications] Thoma-Uszynski,S.: "Activation of Toll-like receptor 2 on human dendritic cells triggers induction of IL-12 but IL-10."J.Immunol.. 165. 3804-3810 (2000)
• [Publications] Tapping,R.I.: "Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides."J.Immunol.. 165. 5780-5787 (2000)
• [Publications] Fukuoka M: "Anti-adhesive function of CD43 130 kDa glycoform expressed in CD4 Tlymphocyte clones and in transfectant cell lines."Blood. 96. 4267-4275 (2000)
• [Publications] Lien,E.: "A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/Toll-like receptor 4 signaling pathway "J.Biol.Chem.. 276. 1873-1880 (2000)