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4 results on '"Hirotani, Tomonori"'

1. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction

Author

Uematsu, Satoshi, primary, Sato, Shintaro, additional, Yamamoto, Masahiro, additional, Hirotani, Tomonori, additional, Kato, Hiroki, additional, Takeshita, Fumihiko, additional, Matsuda, Michiyuki, additional, Coban, Cevayir, additional, Ishii, Ken J., additional, Kawai, Taro, additional, Takeuchi, Osamu, additional, and Akira, Shizuo, additional

Published
2005
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2. Hepatoma‐derived growth factor induces tumorigenesis in vivo through both direct angiogenic activity and induction of vascular endothelial growth factor

Author

Okuda, Yorihide, primary, Nakamura, Hideji, additional, Yoshida, Kenya, additional, Enomoto, Hirayuki, additional, Uyama, Hirokazu, additional, Hirotani, Tomonori, additional, Funamoto, Masanobu, additional, Ito, Hiroaki, additional, Everett, Allen D, additional, Hada, Toshikazu, additional, and Kawase, Ichiro, additional

Published
2003
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3. Hepatoma‐derived growth factor induces tumorigenesis in vivothrough both direct angiogenic activity and induction of vascular endothelial growth factor

Author

Okuda, Yorihide, Nakamura, Hideji, Yoshida, Kenya, Enomoto, Hirayuki, Uyama, Hirokazu, Hirotani, Tomonori, Funamoto, Masanobu, Ito, Hiroaki, Everett, Allen D, Hada, Toshikazu, and Kawase, Ichiro

Abstract

Hepatoma‐derived growth factor (HDGF) is highly expressed in tumor cells, and stimulates their proliferation. In the present study, we investigated the role of HDGF in tumorigenesis and elucidated the mechanism of action. Stable transfectants of NIH3T3 cells overexpressing HDGF did not show significant anchorage‐independent growth in soft agar assay. However, these stable transfectants overexpressing HDGF generated sarcomatous tumors in nude mice. These tumors were red‐colored macroscopically, and histologically showed a rich vascularity. Immunohistochemical analysis using CD31 antibody showed new vessel formation. Recombinant HDGF stimulated proliferation of human umbilical vein endothelial cells in a dose‐dependent manner, and stimulated tubule formation. Furthermore, vascular endothelial growth factor (VEGF) was detected immunohistochemically in the tumor tissues. Transient expression of HDGF induced both VEGFgene and protein expression as demonstrated by a reporter assay using VEGFgene promoter. The administration of anti‐VEGF neutralizing antibody significantly suppressed, but did not block, the tumor growth of HDGF‐overexpressing cells in nude mice. Thus, these findings suggested that HDGF‐induced tumor formation in vivoinvolves induction of VEGF as well as direct angiogenic activity.

Published
2003
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4. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction.

Author

Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, Matsuda M, Coban C, Ishii KJ, Kawai T, Takeuchi O, and Akira S

Subjects
Adaptor Proteins, Signal Transducing, Animals, Antigens, Differentiation metabolism, Cell Line, Gene Expression Regulation genetics, Gene Expression Regulation physiology, Humans, Interferon Regulatory Factor-7, Interleukin-1 Receptor-Associated Kinases, Mice, Mice, Knockout, Mitogen-Activated Protein Kinases metabolism, Myeloid Differentiation Factor 88, NF-kappa B metabolism, Plasma Cells physiology, Protein Kinases genetics, Receptors, Immunologic metabolism, Receptors, Tumor Necrosis Factor metabolism, Signal Transduction genetics, TNF Receptor-Associated Factor 6 metabolism, Toll-Like Receptor 7, Toll-Like Receptor 9, DNA-Binding Proteins metabolism, Dendritic Cells physiology, Interferon-alpha biosynthesis, Membrane Glycoproteins metabolism, Protein Kinases metabolism, Receptors, Cell Surface metabolism, Signal Transduction physiology
Abstract

Toll-like receptors (TLRs) recognize microbial pathogens and trigger innate immune responses. Among TLR family members, TLR7, TLR8, and TLR9 induce interferon (IFN)-alpha in plasmacytoid dendritic cells (pDCs). This induction requires the formation of a complex consisting of the adaptor MyD88, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and IFN regulatory factor (IRF) 7. Here we show an essential role of IL-1 receptor-associated kinase (IRAK)-1 in TLR7- and TLR9-mediated IRF7 signaling pathway. IRAK-1 directly bound and phosphorylated IRF7 in vitro. The kinase activity of IRAK-1 was necessary for transcriptional activation of IRF7. TLR7- and TLR9-mediated IFN-alpha production was abolished in Irak-1-deficient mice, whereas inflammatory cytokine production was not impaired. Despite normal activation of NF-kappaB and mitogen-activated protein kinases, IRF7 was not activated by a TLR9 ligand in Irak-1-deficient pDCs. These results indicated that IRAK-1 is a specific regulator for TLR7- and TLR9-mediated IFN-alpha induction in pDCs.

Published
2005
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