2001 Fiscal Year Annual Research Report

新しいウイルスベクター発現サイトカインを用いた動物の免疫誘導法の開発

Research Project

Project/Area Number	11556058
Research Institution	The University of Tokyo
Principal Investigator	甲斐知恵子東京大学, 医科学研究所, 教授 (10167330)
Co-Investigator(Kenkyū-buntansha)	小原恭子東京大学, 医科学研究所, 講師 (20225478) 中山裕之東京大学, 農学生命科学研究所, 助教授 (40155891) 辻本元東京大学, 農学生命科学研究所, 教授 (60163804) 遠藤泰之東京大学, 医科学研究所, 助手 (90332600) 三浦竜一東京大学, 医科学研究所, 助手 (00322074)
Keywords	サイトカイン / イヌ / センダイウイルス / GM-CSF / IL-8
Research Abstract	本研究の目的は、まず新しい組換え蛋白発現システムである組換えセンダイウイルス発現系を用いてサイトカインを発現させ、in vitro並びにin vivoでの生物活性を検索することである。続いて、活性が確認できたサイトカインでサイトカインネットワークの基礎的研究を行い、その基盤の上に蛋白あるいはウイルスベクターの投与による有効なサイトカインアジュバント免疫誘導法の開発に役立てることである。昨年度までにイヌIFNγ、GM-CSF、IL-8、IL-6のcDNAをそれぞれ持つ組換えセンダイウイルスを作出することに成功し、生物活性を示すサイトカインの産生をin vitroで確認することができた。本年度は実際にイヌに投与して、in vivoでの有効性について検索した。 1)イヌGM-CSF組換えセンダイウイルスを接種した発育鶏卵漿尿液より精製したGM-CSFは、イヌ由来骨髄細胞やGM-CSF依存性細胞株(TF-1細胞)の増殖を濃度依存性に誘導した。6頭の健康なイヌに投与したところ、末梢血総白血球、好中球、および単球の顕著な増加が認められた。 2)同様に発現させ精製したイヌIL-8をリーシュマニア原虫感染マウスの皮膚病変部に、感染14日目より5日間に渡って投与したところ、皮膚病変の悪化(拡大)を抑制することが出来た。以上のことから、組換えセンダイウイルス発現系によるイヌサイトカインは、invivoにおいても十分な生物活性を有することが明らかとなった。

Research Products
(24 results)

All Other

All Publications (24 results)

[Publications] Shiotani, M., et al.: "Molecular properties of the matrixprotein(M) gene of the lapinized rinderpest virus"J Vet Med Sci.. 63(7). 801-805 (2001)
[Publications] Ohashi, K. et al.: "Seroepidemiological survey of distemper virus infection in the Caspian Sea and in Lake Baikal"Vet Microbiol.. 28:82(3). 203-210 (2001)
[Publications] Ikeda, Y., et al.: "Seroprevalence of canine distemper virus in cats"Clin Diagn Lab Immunol. 8(3). 641-644 (2001)
[Publications] Ohashi K, et al.: "Properties of a new CDV isolate from a racoon dog (Nyctereutes procyonoides viverrinus) in Japan"Vet Rec.. 3:148(5). 148-150 (2001)
[Publications] Yoneda, M. et al.: "Rinderpest virus H protein : role in determining host range in rabbits"J. Gen. Virol.. (in press). (2002)
[Publications] Jung, J.-Y., et al.: "Picryl chloride-induced contact dermatitis in IQI/Jic male mice"J. Toxicl. Pathol.. 14. 231-236 (2001)
[Publications] Nagata, T., et al.: "Development of apoptosis and changes in lymphocyte subsets in thymus, mesenteric lymph nodes and Peyer s patches of mice orally inoculated with T-2 toxin"Exp. Toxic Pathol.. 53. 309-315 (2001)
[Publications] Suzuki, K., et al.: "Kinetics of matrix metalloproteinases and their regulatory factors in mercuric chrolide-induced tubulointerstitial fibrosis in Brown Norway rats"Exp. Toxic Pathol.. 53. 337-343 (2001)
[Publications] Ueno, M., et al.: "Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine (5AzC)-induced apoptotic process in the rat"Histol. Histopathol.. (In press). (2001)
[Publications] Masuda, K., et al.: "Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica) pollen"J. Vet. Med. Sci.. 63. 79-81 (2001)
[Publications] Maeda, S., et al.: "Molecular cloning of canine thymus and activation-regulated chemokine (TARC) gene and its expression in various tissues"J. Vet. Med. Sci.. 63. 1035-1038 (2001)
[Publications] Masuda, K., et al.: "Seasonal atopic dermatitis in dogs sensitive to a major allergen of Japanese cedar (Cryptomeria japonica) pollen"Vet. Dermatol.. (In press). (2001)
[Publications] Ishizaka, K., et al.: "Molecular cloning of feline interferon-gamma-inducing factor (interleukin-18) and its expression in various tissues"Vet. Immunol. Immunopathol.. 79. 208-218 (2001)
[Publications] Kobayashi, Y., et al.: "Molecular cloning of feline hepatocyte growth factor (HGF) cDNA"J. Vet. Med. Sci.. 63. 211-214 (2001)
[Publications] Mizuno, T., et al.: "TNF-alpha-induced cell death in feline immunodeficiency virus-infected cells is mediated by the caspase cascade"Virology. 287. 446-455 (2001)
[Publications] Fujino, Y. et al.: "Assignment of the feline Fas ligand gene (TNFSF6) to chromosome F1q12-q13 by fluorescence in situ hybridization"Cytogenet. Cell Genet.. 94. 92-93 (2001)
[Publications] Yamamoto, A. et al.: "Molecular cloning and expression of the cDNA encoding feline granulocyte colony-simulating factor"Gene. 63. 1035-1038 (2001)
[Publications] Mizuno, T., et al.: "Molecular cloning of feline tumor necrosis factor receptor type I (TNFR I) and expression of TNFR I and TNFR II in lymphoid cells in cats"Eur. J. Immunogenetics. (In Press). (2001)
[Publications] Koga, L., et al.: "Nucleotide sequence and expression of the feline vascular endothelial growth factor"J. Vet. Med. Sci.. 64(In Press). (2001)
[Publications] Machida, K., et al.: "Inhibition of Cytochrome C Release in Fas-mediated Signaling by Hepatitis C Viral Proteins in Transgenic Mice Liver"J. Biol. Chem.. 276. 12140-12146 (2001)
[Publications] Ishida, S., et al.: "Icosahedral Hepatitis C Virus Core Particles Detected by Immunoelectron Microscopy and Rotation Technique"Hepatology Research. 20. 335-347 (2001)
[Publications] Tsukiyama-Kohara, T. et al.: "Adipose Tissue Reduction in Mice Lacking the Translational Inhibitor 4E-BP1"Nature Medicine. 7. 1128-1132 (2001)
[Publications] Igarashi, T., et al.: "Rapid and irreversible CD4(+) T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIV(DH12R) is systemic and synchronous"J. Virol.. 76. 379-391 (2002)
[Publications] Igarashi, T., et al.: "Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV) : Implications for HIV-1 infections of humans"Proc. Natl. Acad. Sci. USA. 98. 658-663 (2001)

2001 Fiscal Year Annual Research Report

新しいウイルスベクター発現サイトカインを用いた動物の免疫誘導法の開発

Principal Investigator

甲斐 知恵子 東京大学, 医科学研究所, 教授 (10167330)

Research Products

[Publications] Shiotani, M., et al.: "Molecular properties of the matrixprotein(M) gene of the lapinized rinderpest virus"J Vet Med Sci.. 63(7). 801-805 (2001)

[Publications] Ohashi, K. et al.: "Seroepidemiological survey of distemper virus infection in the Caspian Sea and in Lake Baikal"Vet Microbiol.. 28:82(3). 203-210 (2001)

[Publications] Ikeda, Y., et al.: "Seroprevalence of canine distemper virus in cats"Clin Diagn Lab Immunol. 8(3). 641-644 (2001)

[Publications] Ohashi K, et al.: "Properties of a new CDV isolate from a racoon dog (Nyctereutes procyonoides viverrinus) in Japan"Vet Rec.. 3:148(5). 148-150 (2001)

[Publications] Yoneda, M. et al.: "Rinderpest virus H protein : role in determining host range in rabbits"J. Gen. Virol.. (in press). (2002)

[Publications] Jung, J.-Y., et al.: "Picryl chloride-induced contact dermatitis in IQI/Jic male mice"J. Toxicl. Pathol.. 14. 231-236 (2001)

[Publications] Nagata, T., et al.: "Development of apoptosis and changes in lymphocyte subsets in thymus, mesenteric lymph nodes and Peyer s patches of mice orally inoculated with T-2 toxin"Exp. Toxic Pathol.. 53. 309-315 (2001)

[Publications] Suzuki, K., et al.: "Kinetics of matrix metalloproteinases and their regulatory factors in mercuric chrolide-induced tubulointerstitial fibrosis in Brown Norway rats"Exp. Toxic Pathol.. 53. 337-343 (2001)

[Publications] Ueno, M., et al.: "Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine (5AzC)-induced apoptotic process in the rat"Histol. Histopathol.. (In press). (2001)

[Publications] Masuda, K., et al.: "Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica) pollen"J. Vet. Med. Sci.. 63. 79-81 (2001)

[Publications] Maeda, S., et al.: "Molecular cloning of canine thymus and activation-regulated chemokine (TARC) gene and its expression in various tissues"J. Vet. Med. Sci.. 63. 1035-1038 (2001)

[Publications] Masuda, K., et al.: "Seasonal atopic dermatitis in dogs sensitive to a major allergen of Japanese cedar (Cryptomeria japonica) pollen"Vet. Dermatol.. (In press). (2001)

[Publications] Ishizaka, K., et al.: "Molecular cloning of feline interferon-gamma-inducing factor (interleukin-18) and its expression in various tissues"Vet. Immunol. Immunopathol.. 79. 208-218 (2001)

[Publications] Kobayashi, Y., et al.: "Molecular cloning of feline hepatocyte growth factor (HGF) cDNA"J. Vet. Med. Sci.. 63. 211-214 (2001)

[Publications] Mizuno, T., et al.: "TNF-alpha-induced cell death in feline immunodeficiency virus-infected cells is mediated by the caspase cascade"Virology. 287. 446-455 (2001)

[Publications] Fujino, Y. et al.: "Assignment of the feline Fas ligand gene (TNFSF6) to chromosome F1q12-q13 by fluorescence in situ hybridization"Cytogenet. Cell Genet.. 94. 92-93 (2001)

[Publications] Yamamoto, A. et al.: "Molecular cloning and expression of the cDNA encoding feline granulocyte colony-simulating factor"Gene. 63. 1035-1038 (2001)

[Publications] Mizuno, T., et al.: "Molecular cloning of feline tumor necrosis factor receptor type I (TNFR I) and expression of TNFR I and TNFR II in lymphoid cells in cats"Eur. J. Immunogenetics. (In Press). (2001)

[Publications] Koga, L., et al.: "Nucleotide sequence and expression of the feline vascular endothelial growth factor"J. Vet. Med. Sci.. 64(In Press). (2001)

[Publications] Machida, K., et al.: "Inhibition of Cytochrome C Release in Fas-mediated Signaling by Hepatitis C Viral Proteins in Transgenic Mice Liver"J. Biol. Chem.. 276. 12140-12146 (2001)

[Publications] Ishida, S., et al.: "Icosahedral Hepatitis C Virus Core Particles Detected by Immunoelectron Microscopy and Rotation Technique"Hepatology Research. 20. 335-347 (2001)

[Publications] Tsukiyama-Kohara, T. et al.: "Adipose Tissue Reduction in Mice Lacking the Translational Inhibitor 4E-BP1"Nature Medicine. 7. 1128-1132 (2001)

[Publications] Igarashi, T., et al.: "Rapid and irreversible CD4(+) T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIV(DH12R) is systemic and synchronous"J. Virol.. 76. 379-391 (2002)

甲斐知恵子東京大学, 医科学研究所, 教授 (10167330)