2003 Fiscal Year Final Research Report Summary
Identificaion of compounds acting innate immunity using a newly established in vitro screen
| Project/Area Number |
13557200
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
KURATA Shoichiro Tohoku University, Graduate School of Parmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (90221944)
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| Co-Investigator(Kenkyū-buntansha) |
KUBODERA Noboru Chugai Pharmaceutical Co., Ltd., Planning Dept., Senior Manager, 製品企画部・企画推進担当部, 部長(研究職)
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| Project Period (FY) |
2001 – 2003
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| Keywords | innate immunity / screening / chenokine |
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| Research Abstract |
Innate immunity is the first line of defense against infectious microorganisms, and the basic mechanisms of pathogen recognition and activation of the response are evolutionary conserved. In Mammals, the innate immune response is required in combination with antigen-specific recognition for the activation of the adaptive immunity. Therefore, innate immunity is one of the pharmaceutical targets for the development of immune regulators. In this study, for the purpose of pharmaceutical screening, we established an in vitro culture based on innate immune response of Drosophila. The in vitro system is capable of measuring the lipopolysacharide (LPS)-dependent activation of the imd pathway that shows similarity to tumor necrosis factor (TNF) signaling pathway in mammals. From the screening with about 1,000 samples, we found that a cyclopentanediol derivative inhibits the LPS-dependent activation of the imd pathway. The cyclopentanediol derivative found to inhibit intracellular signaling cascade of the imd pathway from an adaptor protein called imd to Relish transcriptional factor. Because the intracellular signaling cascade of the imd pathway shows similarity to tumor necrosis factor (TNF) signaling pathway in mammals, we investigated whether the cyclopentanediol derivative inhibits human TNF signaling pathway, one of the innate immune response in human. We found that the cyclopentanediol derivative inhibit TNF-dependent induction of chemokines in human umbilical vein endothelial cells (HUVEC). These results suggest that the newly established system is useful for pharmaceutical screening in identification of compounds which act on innate immunity.
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Research Products
(13 results)
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[Publications] Punzo, C., Plaza, S., Seimiya, M., Kurata, S., Schnupf, P., Jager, J., Gehring, W.J.: "eyeless and twin of eyeless conservations and differences in Drosophila melanogaster"Development. (印刷中).
Description
「研究成果報告書概要(和文)」より
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[Publications] Yajima, M., Takada, M., Takahashi, N., Kikuchi, H., Natori, S., Oshima, Y., Kurata, S.: "A newly established in vitro culture using transgenic Drosophila revealed functional coupling between the phospholipase A2-generated Fatty acid cascade and lipopolysaccharide-dependent activation of the imd pathway in insect immunity."Biochem.J.. 371. 205-210 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Takehana, A., Katsuyama, T., Yano, T., Oshima, Y., Takada, H., Aigaki, T., Kurata, S.: "Overexpression of a pattern recognition receptor, peptidoglycan recognition protein-LE, activates Imd/Relish-mediated antibacterial defense and prophenoloxidase cascade in Drosophila larvae"Proc.Natl.Acad.Sci.USA.. 99. 13705-13710 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Ikejima, M., Nozaki, T., Kurata, S., Natori, S., Esumi, H., Sugimura, T., Masutani, M.: "Purification and characterization of poly(ADP-ribose) polymerase cDNA from Sarcophaga peregrina"Proc.Japan Acad.. 78. 282-285 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Takehana, A., Katsuyama, T., Yano, T., Oshima, Y., Takada, H., Aigaki, T., Kurata, S.: "Overexpression of a pattern recognition receptor, peptidoglycan recognition protein-LE, activates Imd/Relish-mediated antibacterial defense and prophenoloxidase cascade in Drosophila larvae."Proc.Natl.Acad.Sci.USA. 99. 13705-13710 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ikejima, M., Nozaki, T., Kurata, S., Natori, S., Esumi, H., Sugimura, T., Masutani, M.: "Purification and characterization of poly(ADP-ribose) polymerase cDNA from Sarcophaga peregrina."Proc.Japan Acad.. 78. 282-285 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yajima, M., Takada, M., Takahashi, N., Kikuchi, H., Natori, S., Oshima, Y., Kurata, S.: "A newly established in vitro culture using transgenic Drosophila revealed functional coupling between the phospholipase AZ-generated fatty acid cascade and lipopolysaccharide-dependent activation of the imd pathway in insect immunity."Biochem.J.. 371. 205-210 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Punzo, C., Plaza, S., Seimiya, M., Kurata, S., Schnupf, P., Jager, J., Gehring, W.J.: "Eyeless and twin of eyeless conservations and differences in Drosophila melanogaster."Development. (in press).
Description
「研究成果報告書概要(欧文)」より
