| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DCs), e.g. Langerhans cells (LCs), it also stimulates some LCs into maturation after irradiation in vivo. To analyze its reciprocal effects on DCs, we elucidated the direct effect of UVB on DCs in vitro using human monocyte-derived DCs (MoDCs). UVB from 50 to 200 J/m^2 stimulated the maturation of MoDCs with 1) augmented expression of co-stimulatory molecules such as CD86 and HLA-DR, 2) enhanced production of IL-1β, IL-6, IL-8, IL-10 and TNF-α at both the mRNA and protein levels, and 3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDCs after UVB demonstrated a dose-dependent phosphorylation of p38-and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPKs), but not that of extracellular signal-regulated kinases (ERK). P38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDCs. Interestingly, MoDCs that had undergone apoptosis exhibited an augmented expression of HLA-DR without up-regulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDCs, depending on the dosage, mainly via the p38 MAPK-pathway.
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