Analysis of the pathomechanism of the demyelinating diseases and the searach for the therapy
| Project/Area Number |
07670373
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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 |
Immunology
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| Research Institution | KYUSHU UNIVERISTY |
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Principal Investigator |
HARA Hideo Kyushu Univ.Medicine lecturer, 医学部, 助手 (00260381)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Takeshi Kyushu Univ.Professor, 生体防御医学研究所, 教授 (40028684)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | HTLV-I / rolipram / ICAM1 / gag / HTLV-1 / TCR / Vβ / ICAM-I / 細胞内シグナル |
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| Research Abstract |
Previous studies reported that production of proinflammatory cytokines, such as TNF-alpha and IFN-gamma, were increased in the serum and the CSF of HAM patients. These cytokines may play an important role in the pathogenesis of HAM/TSP.We examined the effect of PDE-IV inhibitor rolipram on the cytokines production in HTLV-I infected cell lines and PBMCs of HAM patients. PBMCs and HTLV-I infected T cell lines (HUT102, MT2) were cultured with different dose of rolipram in 10% FCS/RPMI1640. Supernatants of cultured cells were harvested after five days. Cytokines were determined by ELISA kits for TNF-alpha, INF-gamma, TGF-beta. RNA were extracted from the cultured PBMSCs and T cell lines. cDNA was synthesized and amplified with primers specific for TNF-alpha, EFN-gamma, TGF-beta by RT-PCR.Rolipram inhibited TNF-alpha production by PBMCs from all HAM patients and HUT102 in dose dependent manner. Production of IFN-gamma was less strongly suppressed in some HAM patients. Concentration of TGF-beta in culture supernatants was not influenced by rolipram. These findings suggest the possibility of rolipram as potential therapy for HAM/TSP.
Intercellular adhesion molecule 1 (ICAM 1) is an inducible protein ligand which is up-regulated during inflammation and is either not consitutively expressed or expressed at low levels. The expression of ICAM1 is increased HTLV-I infected T cell lines as well as in CD4+ T cells of peripheral blood lymphocytes (PBLs) from HAM/TSP patients. After PBLs of HAM patients were cultured in the presence of stimulating anti-ICAM1 antibody, the expression of HTLV-I gag protein in PBLs was observed by the immuno-histostainning and western bloting using HTLV-I antigen specific mouse monoclonal antibody. These data suggested that the signal transduction via adhesion molecule ICAM1 could induce the transcription of HTLV-I gene and this might play an important role in the pathogenesis of HAM/TSP.
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Report
(3 results)
Research Products
(17 results)
