Toshio Hirano

Summary

Affiliation: Osaka University
Country: Japan

Publications

  1. pmc A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis
    Toru Atsumi
    Department of Molecular Oncology C7, Graduate School of Medicine, Osaka University, Suita, Japan
    J Exp Med 196:979-90. 2002
  2. ncbi request reprint Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function
    Hidemitsu Kitamura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230 0045, Japan
    Nat Immunol 7:971-7. 2006
  3. pmc A Four-Step Model for the IL-6 Amplifier, a Regulator of Chronic Inflammations in Tissue-Specific MHC Class II-Associated Autoimmune Diseases
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Osaka University Osaka, Japan
    Front Immunol 2:22. 2011
  4. pmc Zinc is a novel intracellular second messenger
    Satoru Yamasaki
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
    J Cell Biol 177:637-45. 2007
  5. pmc Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction
    Keigo Nishida
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230 0045, Japan
    J Exp Med 206:1351-64. 2009
  6. pmc Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Osaka University, Osaka 565 0871, Japan
    J Exp Med 208:103-14. 2011
  7. pmc The zinc transporter SLC39A14/ZIP14 controls G-protein coupled receptor-mediated signaling required for systemic growth
    Shintaro Hojyo
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Suehiro, Tsurumi, Yokohama, Kanagawa, Japan
    PLoS ONE 6:e18059. 2011
  8. pmc Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells
    Shin ichiro Sawa
    Laboratory of Developmental Immunology, Graduate School of Frontier Bioscience and Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
    J Exp Med 203:1459-70. 2006
  9. pmc STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension
    Chiemi Miyagi
    Dept of Molecular Oncology C7, Graduate School of Medicine, Osaka University, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    J Cell Biol 166:975-81. 2004
  10. pmc A novel role of the L-type calcium channel α1D subunit as a gatekeeper for intracellular zinc signaling: zinc wave
    Satoru Yamasaki
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology RCAI, Yokohama, Kanagawa, Japan
    PLoS ONE 7:e39654. 2012

Detail Information

Publications118 found, 100 shown here

  1. pmc A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis
    Toru Atsumi
    Department of Molecular Oncology C7, Graduate School of Medicine, Osaka University, Suita, Japan
    J Exp Med 196:979-90. 2002
    ..Finally, we showed that disease development was dependent on lymphocytes. These results provide evidence that a point mutation of a cytokine receptor has the potential to induce autoimmune disease...
  2. ncbi request reprint Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function
    Hidemitsu Kitamura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230 0045, Japan
    Nat Immunol 7:971-7. 2006
    ..These results establish a link between Toll-like receptor signaling and zinc homeostasis...
  3. pmc A Four-Step Model for the IL-6 Amplifier, a Regulator of Chronic Inflammations in Tissue-Specific MHC Class II-Associated Autoimmune Diseases
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Osaka University Osaka, Japan
    Front Immunol 2:22. 2011
    ..Thus, the IL-6 amplifier, which is chronically activated by these four events, is a critical regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases...
  4. pmc Zinc is a novel intracellular second messenger
    Satoru Yamasaki
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
    J Cell Biol 177:637-45. 2007
    ..Collectively, our findings indicate that zinc is a novel intracellular second messenger...
  5. pmc Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction
    Keigo Nishida
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230 0045, Japan
    J Exp Med 206:1351-64. 2009
    ..Thus, Znt5 is selectively required for the mast cell-mediated delayed-type allergic response, and it is a novel player in mast cell activation...
  6. pmc Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Osaka University, Osaka 565 0871, Japan
    J Exp Med 208:103-14. 2011
    ..This model provides a possible explanation for why tissue-specific antigens recognized by activated CD4(+) T cells have not been identified in many autoimmune diseases, especially those associated with class II MHC molecules...
  7. pmc The zinc transporter SLC39A14/ZIP14 controls G-protein coupled receptor-mediated signaling required for systemic growth
    Shintaro Hojyo
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Suehiro, Tsurumi, Yokohama, Kanagawa, Japan
    PLoS ONE 6:e18059. 2011
    ..Our data highlight SLC39A14 as an important novel player in GPCR-mediated signaling. In addition, the Slc39a14-KO mice may be useful for studying the GPCR-associated regulation of mammalian systemic growth...
  8. pmc Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells
    Shin ichiro Sawa
    Laboratory of Developmental Immunology, Graduate School of Frontier Bioscience and Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
    J Exp Med 203:1459-70. 2006
    ....
  9. pmc STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension
    Chiemi Miyagi
    Dept of Molecular Oncology C7, Graduate School of Medicine, Osaka University, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    J Cell Biol 166:975-81. 2004
    ....
  10. pmc A novel role of the L-type calcium channel α1D subunit as a gatekeeper for intracellular zinc signaling: zinc wave
    Satoru Yamasaki
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology RCAI, Yokohama, Kanagawa, Japan
    PLoS ONE 7:e39654. 2012
    ..These findings indicated that the LTCC α(1D) subunit located on the ER membrane has a novel function as a gatekeeper for the Zn wave, which is involved in regulating NF-κB signaling and the delayed-type allergic reaction...
  11. pmc Zinc homeostasis and signaling in health and diseases: Zinc signaling
    Toshiyuki Fukada
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, 230 0045, Japan
    J Biol Inorg Chem 16:1123-34. 2011
    ..We have proposed that intracellular Zn signaling falls into two classes, early and late Zn signaling. This review addresses recent findings regarding Zn signaling and its role in physiological processes and pathogenesis...
  12. pmc NetPath: a public resource of curated signal transduction pathways
    Kumaran Kandasamy
    Institute of Bioinformatics, International Tech Park, Bangalore 560066, India
    Genome Biol 11:R3. 2010
    ..We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches...
  13. ncbi request reprint IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state
    Mika Nishihara
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan
    Int Immunol 19:695-702. 2007
    ..Therefore, blockade of IL-6-gp130-STAT3 pathway in CD4+ T cells could be a good target for controlling unwanted Th17-mediated immune responses including autoimmune diseases...
  14. ncbi request reprint Signaling mechanisms through gp130: a model of the cytokine system
    T Hirano
    Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    Cytokine Growth Factor Rev 8:241-52. 1997
    ....
  15. ncbi request reprint Molecular basis underlying functional pleiotropy of cytokines and growth factors
    T Hirano
    Division of Molecular Oncology, Department of Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine C7, 2 2, Yamada oka, Suita, Osaka, 565 0871, Japan
    Biochem Biophys Res Commun 260:303-8. 1999
    ..These mechanisms are part of the molecular basis underlying functional pleiotropy of cytokines and growth factors...
  16. pmc Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir
    Toshio Hirano
    JST CREST, WPI Immunology Frontier Research Center, Osaka University, Japan
    Proc Jpn Acad Ser B Phys Biol Sci 86:717-30. 2010
    ..More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases...
  17. ncbi request reprint Interleukin 6 and its receptor: ten years later
    T Hirano
    Department of Molecular Oncology, Osaka University Medical School, Japan
    Int Rev Immunol 16:249-84. 1998
    ..The deregulated expression of IL-6 and its receptor is involved in a variety of diseases...
  18. doi request reprint IL-6 positively regulates Foxp3+CD8+ T cells in vivo
    Takayuki Nakagawa
    Laboratory of Developmental Immunology and CREST Program of Japan Science and Technology Agency, Graduate School of Frontier Biosciences, Graduate School of Medicine and WPI Immunology Frontier Research Center, Osaka University, Osaka, 565 0871, Japan
    Int Immunol 22:129-39. 2010
    ..These results suggested that Foxp3(+)CD8(+) T cells may develop in response to IL-6 under certain inflammatory conditions in vivo and may regulate some other chronic inflammation diseases...
  19. ncbi request reprint IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation
    Sung Joo Park
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Japan
    J Immunol 173:3844-54. 2004
    ..IL-6 is thus a potent regulator of DC differentiation in vivo, and IL-6-gp130-STAT3 signaling in DCs may represent a critical target for controlling T cell-mediated immune responses in vivo...
  20. ncbi request reprint Zinc is required for Fc epsilon RI-mediated mast cell activation
    Koki Kabu
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology RCAI, Yokohama, Kanagawa, Japan
    J Immunol 177:1296-305. 2006
    ..These results revealed that Zn was involved in multiple steps of FcepsilonRI-induced MC activation and required for degranulation and cytokine production...
  21. ncbi request reprint Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction
    Hideki Ogura
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
    Immunity 29:628-36. 2008
    ..Because this mechanism also enhanced experimental autoimmune encephalomyelitis (EAE) in wild-type mice, it may be a general etiologic process underlying other Th17 cell-mediated autoimmune diseases...
  22. ncbi request reprint Genetic evidence for involvement of maternally derived Wnt canonical signaling in dorsal determination in zebrafish
    Hideaki Nojima
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    Mech Dev 121:371-86. 2004
    ..The tkk locus was mapped to chromosome 16. These data provide genetic evidence that the maternally derived canonical Wnt pathway upstream of beta-catenin is involved in dorsal axis formation in zebrafish...
  23. ncbi request reprint The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis
    Katsuhiko Ishihara
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
    Int Immunol 16:455-65. 2004
    ..gp130F759/F759/pX-Tg is a unique mouse model for RA...
  24. ncbi request reprint Roles of MITF for development of mast cells in mice: effects on both precursors and tissue environments
    Eiichi Morii
    Department of Pathology, Room C2, Osaka University Medical School, Yamada oka 2 2, Suita 565 0871, Japan
    Blood 104:1656-61. 2004
    ..MITF appeared essential for the function of both mast cell precursors and tissue environments for their development...
  25. doi request reprint IFN-gamma expression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death
    Toru Atsumi
    Laboratory of Developmental Immunology and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan
    Int Immunol 21:73-80. 2009
    ....
  26. doi request reprint Hepatic interleukin-7 expression regulates T cell responses
    Yukihisa Sawa
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
    Immunity 30:447-57. 2009
    ....
  27. doi request reprint Gab2, via PI-3K, regulates ARF1 in FcεRI-mediated granule translocation and mast cell degranulation
    Keigo Nishida
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230 0045, Japan
    J Immunol 187:932-41. 2011
    ..ARF1 activity was required for FcεRI-mediated granule translocation. These data indicated that Fyn/Gab2/PI3K/ARF1-mediated signaling is specifically involved in granule translocation and the anaphylaxis response...
  28. pmc TRIF-GEFH1-RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation
    Hokuto Kamon
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan
    EMBO J 25:4108-19. 2006
    ..The activation of GEFH1-RhoB through the TRIF-dependent pathway of LPS in DC might be a critical target for controlling the activation of CD4+ T cells...
  29. ncbi request reprint Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer
    Susumu Yamashita
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
    Nature 429:298-302. 2004
    ..Furthermore, we demonstrate that LIV1 is essential for the nuclear localization of zinc-finger protein Snail, a master regulator of EMT. These results establish a molecular link between STAT3, LIV1 and Snail in EMT...
  30. pmc Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model
    Khie Khiong
    Department of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    J Clin Invest 117:1270-81. 2007
    ..Hence these "memory mutant" mice are a model for human OS; many symptoms of their disease were direct results of the Rag hypomorphism and some were caused by malfunctions of their CD4+ T cells...
  31. ncbi request reprint Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal zone B cells and negatively regulates thymus-independent antigen-2 responses
    Shousaku Itoh
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
    J Immunol 168:5110-6. 2002
    ..Consistent with these results, the Gab1 gene was expressed in marginal zone B cells but not follicular B cells. These results indicated that Gab1 is a unique negative regulator specific for TI-2 responses...
  32. ncbi request reprint IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells
    Hidemitsu Kitamura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama 230 0045, Japan
    Immunity 23:491-502. 2005
    ..Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII alphabeta dimer, Ii, and H2-DM levels in DCs, and suppresses CD4(+) T cell-mediated immune responses...
  33. ncbi request reprint Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses
    Yoshihiro Baba
    Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 1 7 22, Suehirocho, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Nat Immunol 9:81-8. 2008
    ..Thus, STIM1 is key in promoting the Ca2+ influx that is essential for FcepsilonRI-mediated mast cell activation and anaphylaxis...
  34. pmc Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells
    Sho Yamasaki
    Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chuo Ku, Chiba 260 8670, Japan
    Mol Cell Biol 23:2515-29. 2003
    ....
  35. ncbi request reprint Evidence of a novel IL-2/15R beta-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells
    Daisuke Kamimura
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    J Immunol 173:6041-9. 2004
    ....
  36. doi request reprint Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/c-met signaling
    Wataru Shioyama
    Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan
    Circ Res 108:664-75. 2011
    ..Various proangiogenic growth factors regulate angiogenesis and endothelial function. However, the roles of Gab proteins in angiogenesis remain elusive...
  37. ncbi request reprint CD1d-restricted NKT cell activation enhanced homeostatic proliferation of CD8+ T cells in a manner dependent on IL-4
    Naoko Ueda
    Laboratory of Developmental Immunology, Graduate School of Medicine and Graduate School of Frontier Biosciences, Osaka University, 565 0871 Osaka, Japan
    Int Immunol 18:1397-404. 2006
    ..Thus, these results showed the 'involvement' of IL-4 that is produced from activated NKT cells for CD8+ T cell homeostatic proliferation in vivo...
  38. pmc Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane
    Keigo Nishida
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230 0045, Japan
    J Cell Biol 170:115-26. 2005
    ..Finally, we show that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical role in the calcium-independent microtubule-dependent pathway...
  39. ncbi request reprint SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene
    Yoshikazu Nakaoka
    Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Yamadaoka, Osaka, Japan
    J Mol Cell Cardiol 49:157-64. 2010
    ..Collectively, these findings indicate that SHP2 negatively regulates alpha-SKA expression via RhoA inactivation and suggest that SHP2 implicates ERK5 in cardiomyocyte elongation downstream of gp130...
  40. pmc Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway
    Tatsuya Koyama
    Department of Structural Analysis, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita, Osaka, Japan
    J Biol Chem 283:24234-44. 2008
    ..Collectively, these data suggest that the Gab1-SHP2-ERK1/2 signaling pathway comprises an inhibitory axis for IGF-I-dependent myogenic differentiation...
  41. ncbi request reprint Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes
    Yoshikazu Nakaoka
    Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2 2, Yamadaoka, Suita City, Osaka, 565 0871, Japan
    Circ Res 93:221-9. 2003
    ..Taken together, these findings indicate that Gab1-SHP2 interaction plays a crucial role in gp130-dependent longitudinal elongation of cardiomyoctes through activation of ERK5...
  42. ncbi request reprint Stat3 Controls Cell Movements during Zebrafish Gastrulation
    Susumu Yamashita
    Department of Molecular Oncology C 7, Osaka University Graduate School of Medicine, 2 2 Yamada oka, 565 0871, Suita Osaka, Japan
    Dev Cell 2:363-75. 2002
    ..These results reveal a role for Stat3 in controlling cell movements during gastrulation...
  43. pmc Biochemical characterization of human ZIP13 protein: a homo-dimerized zinc transporter involved in the spondylocheiro dysplastic Ehlers-Danlos syndrome
    Bum Ho Bin
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230 0045, Japan
    J Biol Chem 286:40255-65. 2011
    ..This biochemical characterization of the human ZIP13 protein provides important information for further investigations of its structural characteristics and function...
  44. ncbi request reprint Molecular basis of the cell specificity of cytokine action
    Katsuhiko Ishihara
    Department of Molecular Oncology C7, Osaka University Graduate School of Medicine, Suita, Japan
    Biochim Biophys Acta 1592:281-96. 2002
    ..Here we discuss the molecular mechanisms that regulate how the cell specificity of cytokine signals is regulated, especially focusing on the IL-6/gp130 system...
  45. ncbi request reprint Ogon/Secreted Frizzled functions as a negative feedback regulator of Bmp signaling
    Taijiro Yabe
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    Development 130:2705-16. 2003
    ..These data indicate that Ogon/Sizzled functions as a negative regulator of Bmp signaling and reveal a novel role for a sFrp in dorsoventral patterning...
  46. ncbi request reprint Combination treatment with IL-2 and anti-IL-2 mAbs reduces tumor metastasis via NK cell activation
    Gui Hua Jin
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka, Japan
    Int Immunol 20:783-9. 2008
    ..Therefore, combining neutralizing anti-IL-2 mAbs with IL-2 may be clinically useful to effectively enhance IL-2-mediated NK cell activities...
  47. ncbi request reprint IL-6 in autoimmune disease and chronic inflammatory proliferative disease
    Katsuhiko Ishihara
    Department of Molecular Oncology C7, Graduate School of Medicine, Osaka University, 2 2 Yamada Oka Suita, Osaka 565 0871, Japan
    Cytokine Growth Factor Rev 13:357-68. 2002
    ..Here we review the evidence for the involvement of IL-6 in the pathophysiology of autoimmune diseases and chronic inflammatory proliferative diseases (CIPD) and discuss the possible molecular mechanisms of its involvement...
  48. doi request reprint Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier
    Yasunobu Arima
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    Cell 148:447-57. 2012
    ....
  49. ncbi request reprint IL-2 in vivo activities and antitumor efficacy enhanced by an anti-IL-2 mAb
    Daisuke Kamimura
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
    J Immunol 177:306-14. 2006
    ..These results demonstrated IL-2-enhancing effects of the anti-IL-2 mAb in vivo and suggest that combining a neutralizing anti-IL-2 Ab with IL-2 gene delivery might be used effectively to enhance IL-2 functions in clinical applications...
  50. ncbi request reprint [gp130F759 mouse]
    Katsuhiko Ishihara
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Department of Molecular Oncology, Graduate School of Medicine, Osaka University
    Nihon Rinsho 63:68-72. 2005
  51. pmc Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling
    Yoshikazu Nakaoka
    Department of Structural Analysis, National Cardiovascular Center Research Institute, Osaka, Japan
    J Clin Invest 117:1771-81. 2007
    ....
  52. doi request reprint IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses
    Jihye Lee
    Laboratory of Developmental Immunology, Japan Science and Technology Agency Core Research for Engineering, Science, and Technology, Graduate School of Frontier Biosciences, Osaka University, Osaka 565 0871, Japan
    J Immunol 189:1928-36. 2012
    ..From these results, we consider whether the IL-6 amplifier in grafts might be a valuable therapeutic target for the prevention of transplant rejection, including chronic rejection...
  53. ncbi request reprint Gab1 is required for EGF receptor signaling and the transformation by activated ErbB2
    Satoru Yamasaki
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
    Oncogene 22:1546-56. 2003
    ..The data show that Gab1 plays an essential role in EGF-receptor/ErbB-mediated cell proliferation and oncogenesis...
  54. doi request reprint Zinc suppresses Th17 development via inhibition of STAT3 activation
    Chika Kitabayashi
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine and WPI Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    Int Immunol 22:375-86. 2010
    ..Thus, we conclude that Zn suppresses STAT3 activation, which is a critical step for T(h)17 development...
  55. pmc The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways
    Toshiyuki Fukada
    Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Tsurumi, Yokohama, Kanagawa, Japan
    PLoS ONE 3:e3642. 2008
    ..Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown...
  56. doi request reprint Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule
    Toshio Hirano
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565 0871, Japan
    Adv Immunol 97:149-76. 2008
    ..We also review recent progress in uncovering the roles of Zn in the immune system...
  57. doi request reprint Disease-association analysis of an inflammation-related feedback loop
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565 0871, Japan
    Cell Rep 3:946-59. 2013
    ..These results indicate that the IL-6 amplifier is indeed associated with human diseases and disorders and that the identified genes may make for potential therapeutic targets...
  58. doi request reprint IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation
    Jihye Lee
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka, 565 0871, Japan
    Int Immunol 25:319-32. 2013
    ....
  59. ncbi request reprint Requirement of Gab2 for mast cell development and KitL/c-Kit signaling
    Keigo Nishida
    Department of Molecular Oncology C 7, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Blood 99:1866-9. 2002
    ..KitL-induced ERK MAP kinase and Akt activation were impaired in Gab2-deficient BMMCs. These data indicate that Gab2 is required for mast cell development and KitL/c-Kit signaling...
  60. ncbi request reprint Inflammation amplifier, a new paradigm in cancer biology
    Toru Atsumi
    Authors Affiliations JST CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University and JST CREST, Osaka, Japan
    Cancer Res 74:8-14. 2014
    ..Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of cancers...
  61. ncbi request reprint Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells
    Naofumi Kagara
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, and Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
    Cancer Sci 98:692-7. 2007
    ....
  62. ncbi request reprint The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors
    Keigo Nishida
    Department of Molecular Oncology C7, Graduate School of Frontier Biosciences, Osaka University, 2 2 Yamada oka, Suita, Osaka 565 0871
    Cancer Sci 94:1029-33. 2003
    ....
  63. ncbi request reprint Organizer formation and function
    Masahiko Hibi
    Department of Molecular Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
    Results Probl Cell Differ 40:48-71. 2002
  64. ncbi request reprint New IL-6 (gp130) family cytokine members, CLC/NNT1/BSF3 and IL-27
    Masaaki Murakami
    Department of Molecular Oncology, Graduate School of Medicine, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
    Growth Factors 22:75-7. 2004
  65. ncbi request reprint Zinc finger gene fez-like functions in the formation of subplate neurons and thalamocortical axons
    Tustomu Hirata
    Department of Molecular Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    Dev Dyn 230:546-56. 2004
    ....
  66. pmc The pathological and physiological roles of IL-6 amplifier activation
    Masaaki Murakami
    Laboratory of Developmental Immunology, JST CREST, Graduate School of Frontier Biosciences, and WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
    Int J Biol Sci 8:1267-80. 2012
    ....
  67. ncbi request reprint Intracellular zinc homeostasis and zinc signaling
    Masaaki Murakami
    Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
    Cancer Sci 99:1515-22. 2008
    ..In this review article, we will summarize the current understanding of the roles of Zn homeostasis and signaling primarily in immune cells, with a discussion of the contributions of these processes to oncogenesis...
  68. pmc Learning and memory
    H Okano
    Division of Neuroanatomy D12, Department of Neuroscience, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 97:12403-4. 2000
    ....
  69. ncbi request reprint Molecular cloning and expression of an IL-6 signal transducer, gp130
    M Hibi
    Division of Immunology, Osaka University, Japan
    Cell 63:1149-57. 1990
    ..A cloned gp130 could associate with a complex of IL-6 and soluble IL-6-R and transduce the growth signal when expressed in a murine IL-3-dependent cell line...
  70. pmc Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation
    M Itoh
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka 565 0871, Japan
    Mol Cell Biol 20:3695-704. 2000
    ..These results indicate that Gab1 is a common player in a broad range of growth factor and cytokine signaling pathways linking ERK MAP kinase activation...
  71. pmc A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells
    K Nakajima
    Department of Molecular Oncology, Osaka University Medical School, Japan
    EMBO J 15:3651-8. 1996
    ..Stat3 may be a key molecule which determines the cellular decision from cell growth to differentiation in M1 cells...
  72. ncbi request reprint Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
    T Taga
    Division of Immunology, Osaka University, Japan
    Cell 58:573-81. 1989
    ..These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal...
  73. ncbi request reprint IL-6 signal transduction and its physiological roles: the signal orchestration model
    D Kamimura
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
    Rev Physiol Biochem Pharmacol 149:1-38. 2003
    ....
  74. ncbi request reprint Grasp a pTyr-peptide by its SOCS
    Toshio Hirano
    Laboratory of Developmental Immunology, Graduate School of Frontier Bioscience and Graduate School of Medicine, Osaka University, 1 3 Yamadaoka, Suita, Osaka 565 0871, Japan
    Dev Cell 10:542-4. 2006
    ..2006) described the tertiary structure of SOCS3 in complex with a phosphotyrosine-containing peptide from the IL-6 receptor subunit gp130, and they identified the specific amino acids that are critical for binding...
  75. ncbi request reprint Crystallographic studies on human BST-1/CD157 with ADP-ribosyl cyclase and NAD glycohydrolase activities
    Sumie Yamamoto-Katayama
    Department of Molecular Biology, Research Institute BERI, Suita City, Osaka, Japan
    J Mol Biol 316:711-23. 2002
    ..The three key residues are invariant among the sequences of BST-1, CD38, and Aplysia cyclase, and hence this substrate recognition mode and catalytic scheme appear to be common in the cyclase family...
  76. ncbi request reprint A novel repressor-type homeobox gene, ved, is involved in dharma/bozozok-mediated dorsal organizer formation in zebrafish
    Takashi Shimizu
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
    Mech Dev 118:125-38. 2002
    ..These results suggest that ved is a target for the repressor Dha/Boz. Ved functions redundantly with vox/vega1 and vent/vega2 to restrict the organizer domain...
  77. ncbi request reprint Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors
    K Nishida
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
    Blood 93:1809-16. 1999
    ..Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals...
  78. ncbi request reprint Dissection of signaling cascades through gp130 in vivo: reciprocal roles for STAT3- and SHP2-mediated signals in immune responses
    T Ohtani
    Division of Molecular Oncology C7, Biomedical Research Center, Osaka University Graduate School of Medicine, Japan
    Immunity 12:95-105. 2000
    ..These results indicate that the balance of positive and negative signals generated through gp130 regulates the immune responses...
  79. ncbi request reprint Autoregulation of the Stat3 gene through cooperation with a cAMP-responsive element-binding protein
    M Ichiba
    Division of Molecular Oncology, Department of Oncology, Biomedical Research Center, Osaka University Medical School, 2 2 Yamadaoka, Suita City, Osaka 565, Japan
    J Biol Chem 273:6132-8. 1998
    ..This regulatory mechanism is similar to that of the junB gene, which is activated by IL-6 through the junB IL-6RE, which contains a low affinity STAT3-binding site and a CRE-like site...
  80. ncbi request reprint Human BST-1 expressed on myeloid cells functions as a receptor molecule
    Y Okuyama
    Department of Molecular Oncology, Osaka University Medical School, Japan
    Biochem Biophys Res Commun 228:838-45. 1996
    ..These results suggest that BST-1 can deliver signals into cells and function as a receptor...
  81. pmc STAT3 is required for the gp130-mediated full activation of the c-myc gene
    N Kiuchi
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka 565 0871, Japan
    J Exp Med 189:63-73. 1999
    ..This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene...
  82. ncbi request reprint Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis
    T Shirogane
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Japan
    Immunity 11:709-19. 1999
    ..These results indicate that Pim-family proteins play crucial roles in gp130-mediated cell proliferation and explain the synergy between Pim and c-Myc proteins in cell proliferation and lymphomagenesis...
  83. pmc Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis
    T Sugita
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    J Exp Med 171:2001-9. 1990
    ..Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas...
  84. ncbi request reprint Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK
    M Takahashi-Tezuka
    Department of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    Oncogene 14:2273-82. 1997
    ..Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs...
  85. ncbi request reprint Regulation of Pim-1 by Hsp90
    K Mizuno
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2 2 Yamada oka, Suita, Osaka, 565 0871, Japan
    Biochem Biophys Res Commun 281:663-9. 2001
    ..These results indicate that Hsp90 is coordinately regulated with Pim-1 and is involved in the stabilization and function of Pim-1...
  86. ncbi request reprint Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses
    M Itoh
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    J Immunol 161:3974-83. 1998
    ..These results indicate that BST-1 has roles in B cell development and Ab production in vivo...
  87. ncbi request reprint Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility
    D Kamimura
    Department of Molecular Oncology C7, Osaka University Graduate School of Medicine, 2 2 Yamada oka, Suita, Osaka 565 0871, Japan
    Genes Immun 3:136-43. 2002
    ....
  88. ncbi request reprint Genomic structure of human BST-1
    O Muraoka
    Department of Molecular Oncology, Osaka University Medical School, Japan
    Immunol Lett 54:1-4. 1996
    ..The flanking region of the BST-1 gene contained several potential binding sites for nuclear factors, NF-kappa B, p53, NF-IL6, CREB, PEA3, E2A, C/EBP, AP3, AP2 and SP1 and consensus sequences for gamma-IRE and ISRE like element...
  89. pmc BST-1, a surface molecule of bone marrow stromal cell lines that facilitates pre-B-cell growth
    T Kaisho
    Division of Molecular Oncology, Osaka University Medical School, Japan
    Proc Natl Acad Sci U S A 91:5325-9. 1994
    ....
  90. ncbi request reprint Stage-specific expression of mouse BST-1/BP-3 on the early B and T cell progenitors prior to gene rearrangement of antigen receptor
    K Ishihara
    Department of Molecular Oncology, Osaka University Medical School, Japan
    Int Immunol 8:1395-404. 1996
    ..These results showed that murine BST-1 is a useful marker for lymphoid progenitor cells initiating gene rearrangement of their antigen receptors...
  91. ncbi request reprint Molecular cloning of murine BST-1 having homology with CD38 and Aplysia ADP-ribosyl cyclase
    M Itoh
    Division of Molecular Oncology, Osaka University Medical School, Japan
    Biochem Biophys Res Commun 203:1309-17. 1994
    ..Restriction fragment length polymorphism (RFLP) was shown in BALB/c, DBA/2 and NZB vs C57BL/6, A/J, CBA/N, NZW, BXSB and MRL/lpr. RFLP was mapped to the 5' portion of the murine BST-1 gene...
  92. ncbi request reprint Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis
    B O Lee
    Osaka University Medical School, Japan
    Arthritis Rheum 39:629-37. 1996
    ..To investigate the pathophysiologic roles of BST-1 in RA, we established an enzyme-linked immunosorbent assay (ELISA) system to detect the soluble form of BST-1 (sBST-1) and examined levels of sBST-1 in the sera of RA patients...
  93. pmc Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice
    S Suematsu
    Division of Immunology, Osaka University, Japan
    Proc Natl Acad Sci U S A 89:232-5. 1992
    ..These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development...
  94. 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
    ....
  95. pmc Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells
    M Narimatsu
    Department of Molecular Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
    Mol Cell Biol 21:6615-25. 2001
    ..Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells...
  96. ncbi request reprint Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor
    K Yamasaki
    Division of Immunology, Osaka University, Japan
    Science 241:825-8. 1988
    ..The cytoplasmic domain of approximately 82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors...
  97. ncbi request reprint Association of p72 tyrosine kinase with Stat factors and its activation by interleukin-3, interleukin-6, and granulocyte colony-stimulating factor
    T Matsuda
    Division of Molecular Oncology, Osaka University Medical School, Japan
    Blood 83:3457-61. 1994
    ..p72sak may directly activate Stat family proteins or other signal transducing molecules for IL-3, G-CSF, and the IL-6-related cytokine subfamily...
  98. ncbi request reprint Abnormal distribution of IL-6 receptor in aged MRL/lpr mice: elevated expression on B cells and absence on CD4+ cells
    I Kobayashi
    Division of Immunology, Osaka University, Japan
    Int Immunol 4:1407-12. 1992
    ..Our results suggest that overexpression of IL-6R on B cells and absence of IL-6R on peripheral CD4+ cells are concurrent with, or may contribute to, B cell hyperreactivity and T cell abnormality in this strain...
  99. 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...
  100. ncbi request reprint Transcriptional activation of the IL-6 response element in the junB promoter is mediated by multiple Stat family proteins
    Y Fujitani
    Division of Molecular Oncology, Osaka University Medical School, Japan
    Biochem Biophys Res Commun 202:1181-7. 1994
    ..These results indicate that an immediate early signal of IL-6 leading to activation of JRE-IL6 is mediated by STAT family transcription factors...
  101. ncbi request reprint Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors
    M Hibi
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Japan
    Leuk Lymphoma 37:299-307. 2000
    ..These data imply that Gab1 and Gab2 act downstream of a broad range of cytokine and growth factor receptors, as well as T and B antigen receptors, and link these receptors to ERK MAP kinase and biological actions...