2005 Fiscal Year Final Research Report Summary
Genetic immunotherapy of severe immune disease by using human parainfluenza type 2 virus vector
| Project/Area Number |
16590979
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Mie University |
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Principal Investigator |
KAWANO Mitsuo Mie University, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (00234097)
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| Co-Investigator(Kenkyū-buntansha) |
YASUTOMI Yasuhiro Mie University, Graduate School of Medicine, Associate Prof., 大学院・医学系研究科, 助教授 (90281724)
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| Project Period (FY) |
2004 – 2005
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| Keywords | PIV2 / Interleukin-4 / Interleukin-4 antagonist / Asthma / Allergy / Virus vector / Genetic immunotherapy / Th1 / Th2 balance |
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| Research Abstract |
Interleukin-4 (IL-4) is known to induce a shift of the Th1/Th2 balance. Thus, as available tool for the novel genetic immunotherapy of severe immune disease such as asthma, we generated recombinant human parainfluenza type 2 viruses (rPIV2) harboring the gene either for mouse IL-4(mIL-4) or for its antagonist (mIL-4a).
The growth kinetics of these recombinant viruses, rPIV2 (mIL-4) and rPIV2 (mIL-4a) respectively, in tissue culture cells (Vero, BHK or LLC-MK2) was similar to that of parent virus (rPIV2), indicating that expression of mIL-4 or mIL-4a dose not influence the virus replication in tissue culture cells. When the culture media of Vero cells infected with the recombinant viruses (a multiplicity of infection of 3) were assayed by enzyme-linked immunosorbent assay, the amount of mIL-4 and mIL-4a reached a peak level at 48 hr postinfection ; that is
3μg/ml and 5μg/ml respectively. Thus, rPIV2 has a high potential as an vector for expressing foreign genes.
Then, we compared the repli
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cation kinetics of the viruses in the lung of the infected mice by Real-time PCR. After intranasal (IN) administration of the viruses (1x10^7TCID_<50>), rPIV2 (mIL-4a) replicated more efficiently that did rPIV2 while the replication of rPIV2 (mIL-4) was hardly detectable. Nevertheless, there was no clear difference in the extent of inflammation induced by these viruses. On the other hand, the IL-4 level in the bronchopulmonary lymph nodes was reduced after infection with rPIV2 (mIL-4a) while it was increased after infection with rPIV2 (mIL-4). These results suggested that IL-4 plays a suppressive effect on the virus replication in the infected mouse lung.
Next, to test the efficacy of therapeutic value of the recombinant viruses by using the mouse model of ovalbumin-induced asthma, we measured the number of cells and the amount of proteins in the bronchoalveolar lavage of mice after IN administration of the viruses (1x10^7TCID_<50>). These indicators in the rPIV2 (mIL-4a) -infected mice were lower than those in the mice infected with the other viruses by up to 50%. The results of this study thus strongly suggest the potential of rPIV2 (mIL-4a) as a useful tool for the novel genetic immunotherapy of asthma possibly via redressing Th1/Th2 balance. Less
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[Journal Article] Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclastformation of human blood monocytes without cell to cell contact.2005
Author(s)
Nishimura M., Yuasa K., Mori K., Miyamoto N., Ito M., Tsurudome M., Nishio M., Kawano M., Komada H., Uchida A., Ito Y.
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Journal Title
J Orthop Res. 23・5
Pages: 978-987
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclastformation of human blood monocytes without cell to cell contact.2005
Author(s)
Nishimura M., Yuasa K., Mori K., Miyamoto N., Ito M., Tsurudome M., Nishio M., Kawano M., Komada H., Uchida A., Ito Y.
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Journal Title
J Orthop Res. 23(5)
Pages: 979-987
Description
「研究成果報告書概要(欧文)」より
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