| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
To evaluate the effects of Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) on the expression of cytokines in human T-cells, the EBER-expressing plasmid was introduced into three human T-cell lines with site-specific recombination, and the expression of mRNAs of various cytokines was examined with real-time RT-PCR analyses. The expression of EBERs caused the alteration of cytokine expression in a cell line-dependent manner. However, the expression of EBERs in these T-cell lines was generally lower than that in EBV-positive NK/T-cell lines, and only one of three cell lines expressed EBERs at the detectable level with Northern blot analyses. In this cell line, the expression of interleukin-10 was up-regulated and the phosphorylation of dsRNA-dependent protein kinase (PKR) was decreased, indicating that EBERs play a role in the cell line.
On the other hand, EBV-latent membrane protein-1 (LMP1)-expressing human T-cell lines were not established with site-specific recombination. Furthermo
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re, RNA interference to LMP1 in EBV-positive NK/T-cell lines was not successful. Thus, the role of LMP1 in NK/T-cells was still unclear. LMP1 is, however, still a candidate for the responsible gene of cytokinemia, an important pathophysiology of chronic active EBV infection (CAEBV), because the effects of EBERs on expression of Th1 cytokines were not constant as mentioned above.
Approximately one-fourth of CAEBV patients develop vascular lesions with infiltration of EBV-positive lymphoid cells. EBV-positive NK-lymphoma cell lines, SNKs, produced TNFα, which caused the increased expression of ICAM-1 and VCAM-1 in cultured human endothelial cells. Furthermore, SNKs exhibited the increased adhesion to cultured endothelial cells stimulated with TNFα or interleukin-lβ, and the pre-treatment of these cells with anti-VCAM-1-antibodies reduced the cell adhesion. These indicate that the up-regulated expression of VCAM-1 on cytokine-stimulated endothelial cells would be important for the adhesion of EBV-positive NK-cells and might initiate the vascular lesions. Less
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