| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Oral lichen planus is characterized histological by band-like T cells infiltration just under the basal cell layer of mucosal epithelium with unknown etiology. The Killer T and NK cell infiltration into the basal cell layer, indicated degeneration of basal cells. Dendritic cell (DC) found in the lesion of OLP may also important cell elements for controlling the lesion. However, the mechanism of these cells infiltration was not clarified yet. After DC migrated the lesion, DC revealed maturation by local synthesized arachidonate, PGE2. Thus, we made a plan to regulate DC function with suppression of arachidonate synthesis using histone deacethyrase inhibitor.
We first examined cyclooxigenase 2 (COX2) and Phospholipase A2 expression of the OLP lesion, which relate to characteristic white color appearance on oral mucosa. COX2 over expression paralleled to thickness of epithelium and amounts of prickle cells in the epithelium. Clear finding obtained that subgroup specific PLA2, PLA2-V and PL
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A2-X but not for PLA2-IIa, were identified in the epithelium. In vitro experiment demonstrates dose dependent down regulate the PGE2 production by NaBu through the sPLA2 and COX2 expression. However, PGE2 play a role for the epithelial cell repair following epithelial cells received damage by CD8 positive cell and NK cells. More over the COX2 overexpression in the lesions may be related to malignant transformation of OLP. Thus, further experiments required elucidating critical mechanism for controlling the OLP. We also have developed a mouse experimental model of oral mucosal delayed type hyperplasia as a mimic of OLP. In this study, we have valuated the cells and cytokine involve development the OLP lesion for the development of useful treatment system. Our result clearly indicted that NK cell play key role for the early development of the lesion. NK cells deletion with asialo GM1 antibody administration indicated that mouse was clearly showed decrease the severity of DTH due to the disturbance of lymphocytes recruitment. IL-2 and INF-? are major cytokines involved in cell infiltration of the lesion. Less
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