2007 Fiscal Year Final Research Report Summary
Development of therapeutics using interleukin-4 (IL-4) mutein in atherosclerotic mouse model showing Th1-dominant immune response
| Project/Area Number |
16590328
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | University of the Ryukyus (2006-2007)
Kurume University (2004-2005) |
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Principal Investigator |
KATO Seiya University of the Ryukyus, Medicine, Professor (60268844)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHINO Tomoaki Kurume University, Medicine, Lecturer (00261066)
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| Project Period (FY) |
2004 – 2007
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| Keywords | atherosclerosis / inflammation / Th1 response / cytokine / interleukin-4 (IL-4) / mouse / cell culture |
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| Research Abstract |
Inflammatory process of atherosclerosis and its therapeutic implication have been studied. LPA (Lysophosphatidic acid) showed mitogenic activity in the cultured smooth muscle cells as well as induction of NADPH-dependent intracellular oxidative stress, rac-1 (small GTPase) activation, and MCP-1 expression, of which pathway was inhibited by antioxidant and statin. Such in vitro experiments suggested an inflammatory phenotype of vascular cells. Administration of soluble INF_<-γ> receptor in ApoE knockout mice resulted in the suppression of atherogenesis. Moreover, STAT6 knockout mice (B6 backbone) showed not only Th1 shift in the immunological response but the phenotypes of obesity and glucose tolerance, suggesting a close relationship between inflammatory, immunological process and atherosclerosis or metabolic risk factors. Wild type mouse IL-4 gene and its specific cell oriented mutein, Q116E, were sub-cloned into adenovirus-derive expression (shuttle) vector. Primary mouse vascular cells were tested for the changes in inflammatory phenotypes. Development of replication-deficient adenoviral vector was attempting for in vivo experiments. These results further highlighted the importance of inflammatory process of atherosclerosis and suggest the therapeutic implications. We gratefully appreciate for supporting our work and continue to make our best effort to dissolve the pathological problems in human cardiovascular diseases.
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[Journal Article] Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model.2007
Author(s)
Imaoka H, Hoshino T, Takei S, Sakazaki Y, Kinoshita T, Okamoto M, Kawayama T, Yodoi J, Kato S, Iwanaga T, Aizawa H.
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Journal Title
Biochem Biophys Res Commun 360
Pages: 525-530
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Postnatal blocking of interferon-gamma function prevented atheros clerotic plaque formation in apolipoprotein E-knockout mice.2007
Author(s)
Koga M, Kai H, Yasukawa H, Kato S, Yamamoto T, Kawai Y, Kusaba K, Seki Y, Kai M, Egashira K, Kataoka Y, Imaizumi T.
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Journal Title
Hypertens Res 30
Pages: 259-267
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Inhibition of progression and stabilization of plaques by postnatal interferon-gamma function blocking in ApoE-knockout mice.2007
Author(s)
Koga M, Kai H, Yasukawa H, Yamamoto T, Kawai Y, Kato S, Kusaba K, Kai M, Egashira K, Kataoka Y, Imaizumi T.
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Journal Title
Circ Res 101
Pages: 348-356
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Pulmonary inflammation and emphysema : role of the cytokines IL-18and IL-13.2007
Author(s)
Hoshino T, Kato S, Oka N, Imaoka H, Kinoshita T, Takei S, Kitasato Y, Kawayama T, Imaizumi T, Yamada K, Young HA, Aizawa H.
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Journal Title
Am J Respir Crit Care Med 176
Pages: 49-62
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Pitavastatin inhibits lysophosphatidic acid-induced proliferation and monocyte chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing Rac-1-mediated reactive oxygen species generation2007
Author(s)
Kaneyuki U, Ueda S, Yamagishi S, Kato S, Fujimura T, Shibata R, Hayashida A, Yoshimura J, Kojiro M, Oshima K, Okuda S.
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Journal Title
Vascul Pharmacol 46
Pages: 286-292
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Molecular mechanism for elevation of asymmetric dimethylarginine and its role for hypertension in chronic kidney disease.2006
Author(s)
Matsuguma K, Ueda S, Yamagishi S, Matsumoto Y, Kaneyuki U, Shibata R, Fujimura T, Matsuoka H, Kimoto M, Kato S, Imaizumi T, Okuda S.
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Journal Title
J Am Soc Nephrol 17
Pages: 2176-2183
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCSl-deficient mice.2006
Author(s)
Hanada T, Kobayashi T, Chinen T, Saeki K, Takaki H, Koga K, Minoda Y, Sanada T, Yoshioka T, Mimata H, Kato S, Yoshimura A.
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Journal Title
J Exp Med 203
Pages: 1391-1397
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Comparison of histological findings and parathyroid scintigraphy in hemodialysis patients with secondary hyparathyroid glands.2005
Author(s)
Nishida H, Ishibashi M, Hiromatsu Y, Kaida H, Baba K, Miyake I, Ikedo H, Kato S, Fukami K, Iida S, Okuda S.
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Journal Title
Endocr J 52
Pages: 223-228
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Advanced glycation end-products attenuate htiman mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone.2005
Author(s)
Kume S, Kato S, Yamagishi S, Inagaki Y, Ueda S, Arima N, Okawa T, Kojiro M, Nagata K.
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Journal Title
J Bone Miner Res 20
Pages: 1647-1658
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Related Articles, Links Abstract Thioredoxin suppresses airway hyperre sponsiveness and airway inflammation in asthma.2005
Author(s)
Ichiki H, Hoshino T, Kinoshita T, Imaoka H, Kato S, Inoue H, Nakamura H, Yodoi J, Young HA, Aizawa H.
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Journal Title
Biochem Biophys Res Commun 334
Pages: 1141-1148
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] AGEs activate mesangial TGF-β-Smad signaling via an angiotensin II-type I receptor interaction.2004
Author(s)
Fukami K, Ueda S, Yamagishi S, Kato S, Inagaki Y Takeuchi M, Motomiya Y Bucala R, Iida S, Tamaki K, Imaizumi T, Cooper ME, Okuda S.
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Journal Title
Kidney Int 66
Pages: 2137-2147
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Enhanced expression of IL-18 and its receptor in idiopathic pulmonary fibrosis.2004
Author(s)
Eatasato Y, Hoshino T, Okamoto M, Kato S, Koda Y Nagata N, Kinoshita M, Koga H, Yoon DY, Asao H, Ohmoto H, Koga T, Rikimaru T, Aizawa H.
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Journal Title
Am J Resp Cell Mol Biol 31
Pages: 619-625
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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