| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
(1) Expression of SAP/SLAM and EBV reactivation : (1) We characterized the expression of SLAM and SAP in 8 EBV-positive and -negative Burkitt's lymphoma (BL), 5 other B and T, and 2 gastric epitherial cell lines. SLAM was expressed in all tested cell lines, but SAP was expressed in only Daudi, Akata, Jurkat, MT-4 and a gastric epitherial cell line GT38. The SAP expression was analyzed upon reactivation of EBV in Akata, Daudi and GT38 cells. The expression of SAP was reduced dramatically in Daudi and Akata cells by treatment with anti-human immunoglobulins (Ig). TGF-β1 also reduced SAP expression and induced EBV reactivation in Daudi and GT-38 cells, while TGF-β1 did neither suppress SAP nor induce EBV reactivation in Akata cells, which lack TGF-β receptor II. These results indicate that the EBV-reactivation signals such as anti-human Ig and TGF-β1 cross-talk with the SAP signal and that EBV is reactivated simultaneously with the suppression of SAP (acceptable with revison ; Virology J.
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). (2) SLAM signal suppresses cell growth and IL-4 gene expression : We found that an EBV positive lymphoid cell line OB expressed SLAM and anti-SLAM antibody induces the inhibition of cell growth and IL-4 expression but not interferon y expression. These results suggest that SLAM functions an immunological modulator in B cell (in preparation). (3) Diferential expression of SAP in Akata and Daudi clones : We found that SAP expression was different in each clones of Akata and Daudi. The EBV was reactivated by anti-Ig more highly in clones with lower expression of SAP than those of higher expression of SAP (in preparation).
(2) EBV-reactivation signaling : (1) Akata cells have defectiveness of TGF-1 mediated EBV reactivation by the defectiveness of TGF-β receptor II. (2) The AKT/PI3 kinase-pathway up regulates cell growth and spontaneouse EBV reactivation. (3) EA-D molecule is a complex with 58,50,48 and 44 kDa. The 58 and 50 kDa molecules are phosphorilated form, and 48 and 44 kDa molecules are dephosphorilated form and accumurate in EBV reactivated cells. (4) 38 mitogen-activated protein kinase (MAPK) regulates IL-10 gene expression in BL cell lines. We published these results in 4 journals.
(3) A new progress for our future : (2) We determined the C-terminal nucleotide sequences of EBV-LMP1 gene and characterized the sequence variation of Japanese EBV isolates. The results indicate that the Japanese EBV isolates greatly different from the African BL isolates but closely related to the China 1, which is a major strain of Chinese EBV isolates. (2) The China 1 strains of Japanese and Chinese isolates are different with characteristic mutations, respectively. Less
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