S Akira

Summary

Affiliation: Osaka University
Country: Japan

Publications

  1. pmc Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin
    Cevayir Coban
    Exploratory Research for Advanced Technology ERATO, Japan Science and Technology Agency JST, Osaka, Japan
    J Exp Med 201:19-25. 2005
  2. ncbi request reprint Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
  3. ncbi request reprint Functions of toll-like receptors: lessons from KO mice
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    C R Biol 327:581-9. 2004
  4. pmc A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
    Alexis Vandenbon
    Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    BMC Genomics 13:S11. 2012
  5. pmc A Parzen window-based approach for the detection of locally enriched transcription factor binding sites
    Alexis Vandenbon
    Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan
    BMC Bioinformatics 14:26. 2013
  6. ncbi request reprint [Nucleic acids recognition by innate immunity]
    Shizuo Akira
    Laboratory of Host Defense, WPI Immunology Frontier Research Center IFReC, Osaka University Department of Host Defense, Research Institute for Microbial Diseases
    Uirusu 62:39-45. 2012
  7. pmc Impairment of natural killer cytotoxic activity and interferon gamma production in CCAAT/enhancer binding protein gamma-deficient mice
    T Kaisho
    Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663 8501, Japan
    J Exp Med 190:1573-82. 1999
  8. pmc Glucocorticoids synergize with IL-1beta to induce TLR2 expression via MAP Kinase Phosphatase-1-dependent dual Inhibition of MAPK JNK and p38 in epithelial cells
    Akihiro Sakai
    Gonda Department of Cell and Molecular Biology, House Ear Institute, and University of Southern California, Los Angeles, CA 90057, USA
    BMC Mol Biol 5:2. 2004
  9. pmc Toll-like receptor downstream signaling
    Taro Kawai
    ERATO, Japan Science and Technology Agency, Osaka, Japan
    Arthritis Res Ther 7:12-9. 2005
  10. ncbi request reprint Pathogen recognition and innate immunity
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell 124:783-801. 2006

Collaborators

Detail Information

Publications146 found, 100 shown here

  1. pmc Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin
    Cevayir Coban
    Exploratory Research for Advanced Technology ERATO, Japan Science and Technology Agency JST, Osaka, Japan
    J Exp Med 201:19-25. 2005
    ..These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite-host interactions...
  2. ncbi request reprint Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
    ..These findings demonstrate that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense...
  3. ncbi request reprint Functions of toll-like receptors: lessons from KO mice
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    C R Biol 327:581-9. 2004
    ..Besides MyD88, several novel adaptor molecules have recently been identified. Differential utilization of these adaptor molecules may provide the specificity in the TLR signaling...
  4. pmc A novel unbiased measure for motif co-occurrence predicts combinatorial regulation of transcription
    Alexis Vandenbon
    Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    BMC Genomics 13:S11. 2012
    ..Here we propose a new measure for regulatory motif co-occurrence and a new methodology to systematically identify TF pairs significantly co-occurring in a set of promoter sequences...
  5. pmc A Parzen window-based approach for the detection of locally enriched transcription factor binding sites
    Alexis Vandenbon
    Laboratory of Systems Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan
    BMC Bioinformatics 14:26. 2013
    ....
  6. ncbi request reprint [Nucleic acids recognition by innate immunity]
    Shizuo Akira
    Laboratory of Host Defense, WPI Immunology Frontier Research Center IFReC, Osaka University Department of Host Defense, Research Institute for Microbial Diseases
    Uirusu 62:39-45. 2012
    ..Thus, besides direct inhibition of viral replication, this finding reveals that Viperin mediates its antiviral function via the regulation of the TLR7 and TLR9-IRAK1 signaling axis in pDCs...
  7. pmc Impairment of natural killer cytotoxic activity and interferon gamma production in CCAAT/enhancer binding protein gamma-deficient mice
    T Kaisho
    Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663 8501, Japan
    J Exp Med 190:1573-82. 1999
    ..In conclusion, our study reveals that C/EBPgamma is a critical transcription factor involved in the functional maturation of NK cells...
  8. pmc Glucocorticoids synergize with IL-1beta to induce TLR2 expression via MAP Kinase Phosphatase-1-dependent dual Inhibition of MAPK JNK and p38 in epithelial cells
    Akihiro Sakai
    Gonda Department of Cell and Molecular Biology, House Ear Institute, and University of Southern California, Los Angeles, CA 90057, USA
    BMC Mol Biol 5:2. 2004
    ..The increased expression of TLR2 in response to bacteria-induced cytokines has been thought to be crucial for the accelerated immune response and resensitization of epithelial cells to invading pathogens...
  9. pmc Toll-like receptor downstream signaling
    Taro Kawai
    ERATO, Japan Science and Technology Agency, Osaka, Japan
    Arthritis Res Ther 7:12-9. 2005
    ..Taken together, these results indicate that the interaction between individual TLRs and the different combinations of adapters directs appropriate responses against distinct pathogens...
  10. ncbi request reprint Pathogen recognition and innate immunity
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell 124:783-801. 2006
    ..New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity...
  11. ncbi request reprint Toll-like receptors: critical proteins linking innate and acquired immunity
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Nat Immunol 2:675-80. 2001
    ..However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses...
  12. ncbi request reprint The role of Toll-like receptors and MyD88 in innate immune responses
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Endotoxin Res 6:383-7. 2000
    ..We have recently found that the MyD88-independent pathway is involved in LPS-induced maturation of dendritic cells (DCs)...
  13. ncbi request reprint Mammalian Toll-like receptors
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Curr Opin Immunol 15:5-11. 2003
  14. pmc Innate immunity and adjuvants
    Shizuo Akira
    WPI Immunology Frontier Research Center, Osaka University, 3 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    Philos Trans R Soc Lond B Biol Sci 366:2748-55. 2011
    ..I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection...
  15. ncbi request reprint Recognition of pathogen-associated molecular patterns by TLR family
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, SORST of Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Immunol Lett 85:85-95. 2003
    ..These results indicate that TLR3, TLR7 and TLR9 may play an important role in detecting and combating viral infections...
  16. ncbi request reprint Role of adapters in Toll-like receptor signalling
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO of Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Biochem Soc Trans 31:637-42. 2003
    ....
  17. ncbi request reprint Myeloid differentiation factor 88-dependent and -independent pathways in toll-like receptor signaling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and SORST of Japan Science and Technology, Osaka, Japan
    J Infect Dis 187:S356-63. 2003
    ..A recently identified adaptor molecule, Toll-IL receptor domain-containing adaptor protein/MyD88 adaptor-like, may participate in the MyD88-independent pathway...
  18. ncbi request reprint Toll-like receptor signaling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and ERATO of Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Biol Chem 278:38105-8. 2003
  19. ncbi request reprint Toll-like receptors and their signaling mechanisms
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    Scand J Infect Dis 35:555-62. 2003
    ..Characterization of each TLR signaling pathway will reveal the molecular mechanism of self-tolerance as well as cross-tolerance in response to a variety of PAMPs...
  20. pmc Pathogen recognition by innate immunity and its signaling
    Shizuo Akira
    Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
    Proc Jpn Acad Ser B Phys Biol Sci 85:143-56. 2009
    ..This paradigm shift has changed our thinking on the pathogenesis and treatment of infections, immune diseases, allergy, and cancers...
  21. ncbi request reprint Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  22. doi request reprint Potential link between the immune system and metabolism of nucleic acids
    Ken J Ishii
    Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    Curr Opin Immunol 20:524-9. 2008
    ....
  23. ncbi request reprint Toll-like receptors: lessons from knockout mice
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Biochem Soc Trans 28:551-6. 2000
    ..These results show that different TLRs recognize different microbial cell-wall components, and that MyD88 is an essential signalling molecule shared among interleukin-1 receptor/Toll family members...
  24. ncbi request reprint The role of IL-18 in innate immunity
    S Akira
    Department of Host Defense, CREST of Japan Science and Technology Corporation, Research Institute for Microbial Diseases, Osaka University, Suita, 565 0871, Japan
    Curr Opin Immunol 12:59-63. 2000
    ..The IL-18 receptor system and its signal transduction pathway are analogous to those of the IL-1 receptor. Mice deficient in IL-18 have demonstrated its critical role in natural killer cell activity and in vivo Th1 response...
  25. ncbi request reprint TLR signaling
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and ERATO, JST, 3 1 Yamadaoka, Suita, 565 00 Osaka, Japan
    Curr Top Microbiol Immunol 311:1-16. 2006
    ..Thus, mammals make use of both receptor-type and intracellular proteins as detectors of invading pathogens...
  26. ncbi request reprint Endotoxin-induced maturation of MyD88-deficient dendritic cells
    T Kaisho
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Immunol 166:5688-94. 2001
    ..Collectively, the present study provides the first evidence that the MyD88-independent pathway downstream of TLR4 can lead to functional DC maturation, which is critical for a link between innate and adaptive immunity...
  27. ncbi request reprint A Toll-like receptor recognizes bacterial DNA
    H Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Suita
    Nature 408:740-5. 2000
    ..The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA...
  28. ncbi request reprint Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and CREST of Japan Science and Technology Corp, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Int Immunol 12:113-7. 2000
    ..In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components...
  29. ncbi request reprint Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    Immunity 11:443-51. 1999
    ..These results demonstrate that TLR2 and TLR4 recognize different bacterial cell wall components in vivo and TLR2 plays a major role in Gram-positive bacterial recognition...
  30. ncbi request reprint Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes
    T Kawai
    Department of Host Defense, Research Institute for Microbial Diseases, Japan Science and Technology Corporation, Osaka University, Osaka, Japan
    J Immunol 167:5887-94. 2001
    ....
  31. ncbi request reprint The genomic structure and chromosomal localization of the mouse STAT3 gene
    W Shi
    Division of Immunology, Osaka University, Japan
    Int Immunol 8:1205-11. 1996
    ....
  32. ncbi request reprint Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Osaka, Japan
    J Immunol 165:5392-6. 2000
    ..aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4...
  33. ncbi request reprint A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages
    M Matsumoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    J Immunol 163:5039-48. 1999
    ..The Mincle gene locus was mapped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6...
  34. ncbi request reprint Toll-like receptors and their signaling mechanism in innate immunity
    T Kaisho
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita City, Japan
    Acta Odontol Scand 59:124-30. 2001
    ..Here, we describe recent progress in elucidating the function and signaling mechanisms of the TLR family...
  35. ncbi request reprint Discrimination of bacterial lipoproteins by Toll-like receptor 6
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    Int Immunol 13:933-40. 2001
    ..Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria...
  36. ncbi request reprint Mouse proteasomal ATPases Psmc3 and Psmc4: genomic organization and gene targeting
    Y Sakao
    Department of Host Defense, Research Institute for Microbial Diseases, Suita, Osaka, Japan
    Genomics 67:1-7. 2000
    ..These findings indicate that Psmc3 and Psmc4 have similar and essential roles in early embryogenesis and further that both ATPases have noncompensatory functions in vivo...
  37. ncbi request reprint Multi-functional roles of Stat3 revealed by conditional gene targeting
    K Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    Arch Immunol Ther Exp (Warsz) 49:279-83. 2001
    ..By this method, Stat3 was disrupted in several types of tissue, including T cells, macrophages, skin, and mammary gland. Analyses of these Stat3-mutant mice revealed important roles of Stat3 in biological functions in each tissue...
  38. ncbi request reprint Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice
    T Kaisho
    Dept of Host Defense, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3 1, Suita, 565 0871, Osaka, Japan
    Trends Immunol 22:78-83. 2001
    ..Lipopolysaccharide binds TLR4 and can induce DC maturation in the absence of MyD88, whereas CpG DNA binds TLR9 and induces DC maturation in a MyD88-dependent manner...
  39. pmc Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus
    Takayuki Abe
    Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Virol 79:2847-58. 2005
    ....
  40. pmc Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice
    Masaya Kobayashi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Clin Invest 111:1297-308. 2003
    ..Thus, this study clearly established a sequential innate and acquired immune mechanism for the development of Th1-dependent enterocolitis...
  41. ncbi request reprint Cell type-specific involvement of RIG-I in antiviral response
    Hiroki Kato
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Immunity 23:19-28. 2005
    ..In contrast, plasmacytoid DCs, which produce large amounts of IFN-alpha, use the TLR system rather than RIG-I for viral detection. Taken together, RIG-I and the TLR system exert antiviral responses in a cell type-specific manner...
  42. pmc The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function
    K Hoshino
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    J Exp Med 190:1541-8. 1999
    ..In addition, differentiation and function of bone marrow-derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells...
  43. ncbi request reprint Identification of alternative splicing form of Stat2
    T Sugiyama
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    FEBS Lett 381:191-4. 1996
    ..The significance of these spliced forms is discussed...
  44. ncbi request reprint Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice
    K Takeda
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    J Immunol 157:3220-2. 1996
    ..Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6...
  45. ncbi request reprint Roles of Toll-like receptors in innate immune responses
    K Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
    Genes Cells 6:733-42. 2001
    ..The activation of innate immunity then leads to the development of antigen-specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses...
  46. ncbi request reprint Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2: role of N-terminal hydrophobic portion in its multiple functions
    M Nishiguchi
    Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan
    J Immunol 166:2610-6. 2001
    ....
  47. ncbi request reprint TLR signaling pathways
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Semin Immunol 16:3-9. 2004
    ..Thus, TIR domain-containing adaptors provide specificity of TLR signaling...
  48. ncbi request reprint A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA
    Ken J Ishii
    Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Nat Immunol 7:40-8. 2006
    ..These results suggest that both TBK1 and IKKi are required for innate immune activation by B-DNA, which might be important in antiviral innate immunity and other DNA-associated immune disorders...
  49. ncbi request reprint Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nature 420:324-9. 2002
    ..Instead, TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4...
  50. ncbi request reprint The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and Solution Oriented Research for Science and Technology, Japan Science and Technology Corp, Suita, Osaka, Japan
    J Immunol 170:3059-64. 2003
    ..This study demonstrates that the TLR9-MyD88 signaling pathway is essential for all DC responses to both types of CpG DNAs...
  51. pmc IkappaB kinase alpha is essential for mature B cell development and function
    T Kaisho
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    J Exp Med 193:417-26. 2001
    ..Taken together, these results demonstrate that IKKalpha is critically involved in the prevention of cell death and functional development of mature B cells...
  52. ncbi request reprint Toll-like receptors; their physiological role and signal transduction system
    O Takeuchi
    Department of Host Defense, Osaka University, Suita, Japan
    Int Immunopharmacol 1:625-35. 2001
    ..Taken together, TLRs and the downstream signaling pathway play a key role in innate immune recognition and in subsequent activation of adaptive immunity...
  53. ncbi request reprint [Bacterial infections and toll-like receptors]
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    Kekkaku 76:593-600. 2001
    ..However, in LPS signaling MyD88-independent pathway is present in addition to MyD88-dependent pathway...
  54. pmc Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6
    T Nakajima
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Proc Natl Acad Sci U S A 90:2207-11. 1993
    ..Mutation of Thr-235 abolished the ras-dependent activation of NF-IL6. From these results, we conclude that NF-IL6 is regulated through phosphorylation by MAP kinases in response to activated ras...
  55. ncbi request reprint Toll-like receptors as adjuvant receptors
    Tsuneyasu Kaisho
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    Biochim Biophys Acta 1589:1-13. 2002
    ..Understanding the TLR system should offer invaluable opportunity for manipulating host immune responses...
  56. ncbi request reprint Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like re
    Shintaro Sato
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    J Immunol 171:4304-10. 2003
    ..Taken together, these results demonstrate that TRIF associates with TRAF6 and TBK1 independently, and activates two distinct transcription factors, NF-kappaB and IFN regulatory factor-3, respectively...
  57. pmc The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Exp Med 199:1641-50. 2004
    ..Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-beta and IFN-inducible genes in both TLR-stimulated and virus-infected EFs...
  58. pmc Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction
    Satoshi Uematsu
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565 0871, Japan
    J Exp Med 201:915-23. 2005
    ..These results indicated that IRAK-1 is a specific regulator for TLR7- and TLR9-mediated IFN-alpha induction in pDCs...
  59. ncbi request reprint TLR signalling and the function of dendritic cells
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    Chem Immunol Allergy 86:120-35. 2005
    ..Thus, TLRs are critical molecules to induce not only inflammatory responses but also fine-tuned adaptive immune responses depending on invading pathogens...
  60. ncbi request reprint Regulation of innate immune responses by Toll-like receptors
    K Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
    Jpn J Infect Dis 54:209-19. 2001
    ..Progress in elucidating the molecular mechanisms for LPS tolerance has been made through the analysis of TLR-mediated signaling pathways. Thus, the activity for innate immune responses is known to be finely regulated by TLRs...
  61. ncbi request reprint Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages
    T Tanaka
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 80:353-61. 1995
    ..We also demonstrate that NF-IL6 is essential for the induction of G-CSF in macrophages and fibroblasts...
  62. ncbi request reprint Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation
    Katsuaki Hoshino
    Department of Host Defense and Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Int Immunol 14:1225-31. 2002
    ..However, in contrast to TLR4 signaling, TLR9 signaling requires type I IFN signaling for CD40 up-regulation. Taken together, this study demonstrates differential involvement of type I IFN in TLR4- and TLR9-induced effects on DC...
  63. doi request reprint Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9
    Cevayir Coban
    Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    Cell Host Microbe 7:50-61. 2010
    ..The adjuvant function of sHZ was further validated in a canine antiallergen vaccine model. Thus, HZ can influence adaptive immune responses to malaria infection and may have therapeutic value in vaccine adjuvant development...
  64. ncbi request reprint TLR signaling
    T Kawai
    Exploratory Research for Advanced Technology, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell Death Differ 13:816-25. 2006
    ..This review outlines the recent advances in our understanding of TLR-signaling pathways and their roles in immune responses. Further, we also discuss a new concept of TLR-independent mechanisms for recognition of microbial pathogens...
  65. ncbi request reprint Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human
    O Tanabe
    Division of Immunology, Osaka University, Japan
    J Immunol 141:3875-81. 1988
    ..These sequences may play an important role in transcriptional activation of the IL-6 gene...
  66. pmc A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family
    S Akira
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    EMBO J 9:1897-906. 1990
    ....
  67. ncbi request reprint Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Immunol 3:196-200. 2002
    ..Imidazoquinoline-induced signaling events were also abolished in both MyD88- and TLR7-deficient mice...
  68. pmc Analysis of binding site for the novel small-molecule TLR4 signal transduction inhibitor TAK-242 and its therapeutic effect on mouse sepsis model
    K Takashima
    Pharmaceutical Research Division, Pharmacology Research Laboratories I, Takeda Pharmaceutical Company Limited, 2 17 85 Jusohonmachi, Yodogawa ku, Osaka, Japan
    Br J Pharmacol 157:1250-62. 2009
    ..In this study, we investigated the target molecule of TAK-242 and examined its therapeutic effect in a mouse sepsis model...
  69. ncbi request reprint MyD88 as a bottle neck in Toll/IL-1 signaling
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    Curr Top Microbiol Immunol 270:155-67. 2002
    ..Analysis of MyD88-deficient mice revealed its essential role in TLR/IL-1R signaling as well as in both the innate and the adaptive immune response...
  70. ncbi request reprint [Roles of Toll-like receptor in host defense and the mechanism of its signal transduction]
    Osamu Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University
    Nihon Saikingaku Zasshi 59:523-9. 2004
  71. ncbi request reprint Endotoxin can induce MyD88-deficient dendritic cells to support T(h)2 cell differentiation
    Tsuneyasu Kaisho
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Int Immunol 14:695-700. 2002
    ..In vivo experiments with adjuvants also revealed T(h)2-skewed immune responses in MyD88(-/-) mice. These results demonstrate that the MyD88-independent pathway through TLR4 can confer on DC the ability to support T(h)2 immune responses...
  72. ncbi request reprint Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination
    Shohei Koyama
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka, Japan
    J Immunol 179:4711-20. 2007
    ..These results strongly suggest that either the MyD88 or IPS-1 signaling pathway is sufficient for initial antiviral responses, whereas the protective adaptive immune responses to influenza A virus are governed by the TLR7-MyD88 pathway...
  73. ncbi request reprint Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6
    Taro Kawai
    ERATO, Akira Innate Immunity Program, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Immunol 5:1061-8. 2004
    ..These results indicate that TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination...
  74. ncbi request reprint Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Suita, Osaka, Japan
    J Immunol 169:6668-72. 2002
    ..TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway...
  75. ncbi request reprint Essential role of Stat6 in IL-4 signalling
    K Takeda
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Nature 380:627-30. 1996
    ..These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses...
  76. ncbi request reprint Roles of STAT3 defined by tissue-specific gene targeting
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Oncogene 19:2607-11. 2000
    ..Analyses of tissue-specific STAT3-deficient mice indicate that STAT3 plays a crucial role in a variety of biological functions including cell growth, suppression and induction of apoptosis, and cell motility. Oncogene (2000)...
  77. ncbi request reprint Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway
    S Akira
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Cell 77:63-71. 1994
    ....
  78. ncbi request reprint STAT family of transcription factors in cytokine-mediated biological responses
    K Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, and CREST of Japan Science and Technology Corporation, Osaka University, 3 1 Yamada oka, Suita, Osaka, Japan
    Cytokine Growth Factor Rev 11:199-207. 2000
    ..Conditional knockout study of Stat3 demonstrates its critical roles in cytokine-mediated functions in several tissues, including T cells, macrophages, skin, and mammary gland...
  79. ncbi request reprint NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation
    F Nomura
    Department of Host Defense, Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Genes Cells 5:191-202. 2000
    ..Unlike IKK-alpha and IKK-beta, IKK-i phosphorylated Ser36 but not Ser32 in vitro, suggesting that IKK-i activates NF-kappaB by distinct mechanisms from the conventional IKKs...
  80. ncbi request reprint Innate immune recognition of viral infection
    Taro Kawai
    Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Suita, Osaka 565 0871, Japan
    Nat Immunol 7:131-7. 2006
    ..These two classes of pattern-recognition receptor molecules are expressed in different intracellular compartments and induce type I interferon responses via distinct signaling pathways...
  81. ncbi request reprint Interferon response induced by Toll-like receptor signaling
    Osamu Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Endotoxin Res 10:252-6. 2004
    ..These observations demonstrate that IKK-i/TBK1 signaling is essential for both TLR3-dependent and TLR3-independent viral and dsRNA-induced IFN responses...
  82. ncbi request reprint Regulation of lipopolysaccharide-inducible genes by MyD88 and Toll/IL-1 domain containing adaptor inducing IFN-beta
    Tomonori Hirotani
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Biochem Biophys Res Commun 328:383-92. 2005
    ..Genes known to be induced by type I interferons were simply dependent on TRIF for their expression. Taken together, MyD88 and TRIF play both redundant and distinct roles in LPS-induced gene expression...
  83. ncbi request reprint Cutting edge: Role of TANK-binding kinase 1 and inducible IkappaB kinase in IFN responses against viruses in innate immune cells
    Kosuke Matsui
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    J Immunol 177:5785-9. 2006
    ..Thus, these two kinases are essential and compensate each other for the regulation of IFN responses in innate immune cells except plasmacytoid DCs...
  84. ncbi request reprint Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka, Japan
    Nature 430:218-22. 2004
    ....
  85. ncbi request reprint Genetic approaches to the study of Toll-like receptor function
    Osamu Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka, Japan
    Microbes Infect 4:887-95. 2002
    ..Ten members have been reported to date, seven of which were found to recognize discrete bacterial components. Mouse models lacking each TLR and its signaling molecule are useful tools for the analysis of the innate immune system...
  86. ncbi request reprint Lipopolysaccharide-dependent prostaglandin E(2) production is regulated by the glutathione-dependent prostaglandin E(2) synthase gene induced by the Toll-like receptor 4/MyD88/NF-IL6 pathway
    Satoshi Uematsu
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    J Immunol 168:5811-6. 2002
    ..Thus, mPGES is critically involved in the biosynthesis of PGE(2) induced by LPS, but is dispensable for the modulation of inflammatory responses...
  87. doi request reprint Cutting Edge: TLR-Dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-{alpha} production in plasmacytoid dendritic cells
    Yutaro Kumagai
    World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan
    J Immunol 182:3960-4. 2009
    ..These results showed that detection of viruses via TLRs together with a type I IFN feedback system circumvents the requirement for viral replication-dependent recognition in pDCs...
  88. ncbi request reprint TIR domain-containing adaptors define the specificity of TLR signaling
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Mol Immunol 40:861-8. 2004
    ..Indeed, two additional TIR domain-containing adaptors, TIRAP/Mal and TRIF, have recently been identified. Both define the specific biological responses of each TLR...
  89. pmc Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response via MyD88
    Andreas Jung
    WPI Immunology Frontier Research Center, Laboratory of Host Defense, Osaka University, 3 1 Yamada oka, Suita 565 0871, Osaka, Japan
    J Virol 82:196-206. 2008
    ..Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination...
  90. ncbi request reprint [Innate immunity and allergic diseases]
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Disease, Osaka University
    Arerugi 51:352-6. 2002
  91. ncbi request reprint TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Nat Immunol 4:1144-50. 2003
    ..TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling...
  92. ncbi request reprint IL-10-inducible Bcl-3 negatively regulates LPS-induced TNF-alpha production in macrophages
    Hirotaka Kuwata
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Blood 102:4123-9. 2003
    ..These findings suggest that IL-10-induced Bcl-3 is required for suppression of TNF-alpha production in macrophages...
  93. pmc Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis
    S Sano
    Department of Dermatology, Osaka University Medical School, 2 2 Yamadaoka, Suita, Osaka 565 0871, USA
    EMBO J 18:4657-68. 1999
    ..We therefore conclude that Stat3 plays a crucial role in transducing a signal required for migration but not for proliferation of keratinocytes, and that Stat3 is essential for skin remodeling, including hair cycle and wound healing...
  94. ncbi request reprint Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells
    Satoshi Uematsu
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565 0871, Japan
    Nat Immunol 7:868-74. 2006
    ..These data suggest that CD11c+ LPCs, via TLR5, detect and are used by pathogenic bacteria in the intestinal lumen...
  95. ncbi request reprint Cutting edge: cooperation of IPS-1- and TRIF-dependent pathways in poly IC-enhanced antibody production and cytotoxic T cell responses
    Himanshu Kumar
    Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
    J Immunol 180:683-7. 2008
    ..Taken together, these results demonstrate that the adjuvant effects of poly IC require a cooperative activation of TLR and cytoplasmic RNA helicase pathways...
  96. ncbi request reprint The nuclear IkappaB protein IkappaBNS selectively inhibits lipopolysaccharide-induced IL-6 production in macrophages of the colonic lamina propria
    Tomonori Hirotani
    Department of Host Defense, Research Institute for Microbial Diseases, Graduate School of Medicine, Osaka University, Osaka, Japan
    J Immunol 174:3650-7. 2005
    ..Thus, IkappaBNS selectively suppresses LPS-induced IL-6 production in macrophages. This study established that nuclear IkappaB proteins differentially regulate LPS-induced inflammatory cytokine production in macrophages...
  97. ncbi request reprint Toll receptors and pathogen resistance
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and SORST of Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Cell Microbiol 5:143-53. 2003
    ..Thus, individual TLRs may have their own signalling systems that characterize their specific activities...
  98. ncbi request reprint Microbial recognition by Toll-like receptors
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Dermatol Sci 34:73-82. 2004
    ..TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses...
  99. ncbi request reprint Pathological role of Toll-like receptor signaling in cerebral malaria
    Cevayir Coban
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    Int Immunol 19:67-79. 2007
    ..These results strongly suggest that TLR2- and/or TLR9-mediated, MyD88-dependent brain pathogenesis may play a critical role in CM, the lethal complication during PbA infection...
  100. pmc IgG1 plasmacytosis in interleukin 6 transgenic mice
    S Suematsu
    Division of Immunology, Osaka University, Japan
    Proc Natl Acad Sci U S A 86:7547-51. 1989
    ..Other interesting findings in these transgenic mice were the development of mesangio-proliferative glomerulonephritis and an increase in megakaryocytes in bone marrow...
  101. doi request reprint Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 11:123-32. 2009
    ..These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-kappaB activation pathway through linear polyubiquitylation of NEMO...