Yukio Iino
Ajinomoto
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Publication
Featured researches published by Yukio Iino.
Biochemical and Biophysical Research Communications | 2002
Kenji Takehana; Atsushi Konishi; Akiko Oonuki; Misato Noguchi; Koichi Fujita; Yukio Iino; Tsuyoshi Kobayashi
Endothelial cells participate in the inflammatory and immune reactions. Endothelial cell activation is a recurrent phenomenon linked to the pathogenesis of diverse human diseases, such as acute and chronic inflammation and cardiovascular disorders. Pro-inflammatory cytokines (e.g., IL-1, TNF) are well-known activators of endothelial cells, since they strongly induce production of chemokines (e.g., IL-8, MCP-1) and cell adhesion molecules, resulting in an activation of inflammatory transcription factors such as NF-kappaB. We have established a cell-based reporter assay for the NF-kappaB-dependent gene activation in HUVEC. Using this assay system, we have identified a novel synthetic small molecule, APC0576, 5-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine, as an inhibitor of IL-1-induced NF-kappaB-dependent gene activation without any adverse effects on the cell viability. APC0576 represses the IL-1-induced release of chemokines (e.g., IL-8, MCP-1) in HUVEC. This inhibitory effect occurred at the level of mRNA expression. Despite having a strong inhibitory effect on the NF-kappaB-dependent transcriptional activation, APC0576 does not inhibit the IL-1-induced DNA binding of NF-kappaB, degradation of I-kappaB-alpha, or phosphorylation of RelA (p65). Although its molecular mechanism of action is not yet clear, APC0576 is a promising therapeutic candidate for diverse diseases involved in the pathogenic endothelial activation.
Transplantation | 2003
Kenji Yuzawa; Atsushi Konishi; Kenji Takehana; Yukio Iino; Akiko Ohnuki; Tsuyoshi Kobayashi; Katashi Fukao; Nobuhiro Ohkohchi
Background. APC0576, 5-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)-2,2-dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine is a novel synthetic compound with an inhibitory activity on NF-&kgr;B–dependent gene activation and chemokine synthesis in human endothelial cells. This article describes the effect of APC0576 on T-cell–dependent immune functions in vitro and in vivo in primate models, because NF-&kgr;B is known to be one of the potent mediators in T-cell activation. Methods. The effects of APC0576 on interleukin-2 production and proliferative responses in human peripheral blood mononuclear cells were studied under various stimuli with in vitro culture assay. Next, female rhesus monkeys were immunized with tetanus toxoid (TTx), and APC0576 was orally administered for 4 weeks. Serum-specific antibody for TTx was monitored weekly using an enzyme-linked immunosorbent assay, and delayed-type hypersensitivity reaction was examined after 4 weeks of APC0576 treatment. To evaluate the immunosuppressive activity, APC0576 was orally administered for 32 days to rhesus monkeys that received transplants of allogeneic kidney. Results. APC0576 effectively suppressed interleukin-2 production and proliferation in activated human peripheral blood mononuclear cells. Both delayed-type hypersensitivity reaction and specific antibody formation evoked by TTx was significantly and dose-dependently attenuated by 4 weeks treatment of APC0576 without any serious toxicologic signs. Allogeneic kidneys grafted in rhesus monkeys were not rejected and fully functioned during the 32 days of APC0576 treatment, although they were rapidly rejected after the withdrawal of the drug. Conclusions. A novel, orally available immunosuppressive agent, APC0576, effectively inhibited T-cell–based immune responses both in vitro and in vivo. APC0576 may have potential for a therapeutic agent in clinical organ transplantation and various cytokine-mediated diseases.
Archive | 2001
Yukio Iino; Koichi Fujita; Ariko Kodaira; Toshihiro Hatanaka; Kenji Takehana; Tsuyoshi Kobayashi; Atsushi Konishi; Takashi Yamamoto
Archive | 1999
Yukio Iino; Kohichi Fujita; Takashi Tsuji; Ariko Kodaira; Kenji Takehana; Tsuyoshi Kobayashi; Takashi Yamamoto
Archive | 2002
Yukio Iino; Kohichi Fujita; Ariko Kodaira; Toshihiro Hatanaka; Kenji Takehana; Tsuyoshi Kobayashi; Atsushi Konishi; Takashi Yamamoto
Archive | 2002
Ryusuke Hirama; Yukio Iino; Seiji Niwa; Akiyo Yamazaki; 丹羽 誠司; 山▲崎▼ 晶代; 平間 竜介; 飯野 幸生
Archive | 2001
Yukio Iino; Kohichi Fujita; Takashi Tsuji; Ariko Kodaira; Kenji Takehana; Tsuyoshi Kobayashi; Takashi Yamamoto
Archive | 2006
Yukio Iino; Takao Ikenoue; Nobuo Kondo; Hiroyuki Matsueda; Toshihiro Hatanaka; Ryusuke Hirama; Yoko Masuzawa; Fumio Ohta; Akiyo Yamazaki
Archive | 2005
Takao Ikenoue; Yoko Kageyama; Yukio Iino; Nobuo Kondo
Archive | 2002
Fumie Futaki; Yukio Iino; Miki Kobayashi; Yukitane Ono; Kenji Takehana; 二木 史恵; 小林 幹; 小野 幸胤; 竹鼻 健司; 飯野 幸生